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Genes, Volume 6, Issue 3 (September 2015) , Pages 451-934

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Open AccessArticle
Identification of miRNAs Responsive to Botrytis cinerea in Herbaceous Peony (Paeonia lactiflora Pall.) by High-Throughput Sequencing
Genes 2015, 6(3), 918-934; https://doi.org/10.3390/genes6030918 - 18 Sep 2015
Cited by 9 | Viewed by 2160
Abstract
Herbaceous peony (Paeonia lactiflora Pall.), one of the world’s most important ornamental plants, is highly susceptible to Botrytis cinerea, and improving resistance to this pathogenic fungus is a problem yet to be solved. MicroRNAs (miRNAs) play an essential role in resistance [...] Read more.
Herbaceous peony (Paeonia lactiflora Pall.), one of the world’s most important ornamental plants, is highly susceptible to Botrytis cinerea, and improving resistance to this pathogenic fungus is a problem yet to be solved. MicroRNAs (miRNAs) play an essential role in resistance to B. cinerea, but until now, no studies have been reported concerning miRNAs induction in P. lactiflora. Here, we constructed and sequenced two small RNA (sRNA) libraries from two B. cinerea-infected P. lactiflora cultivars (“Zifengyu” and “Dafugui”) with significantly different levels of resistance to B. cinerea, using the Illumina HiSeq 2000 platform. From the raw reads generated, 4,592,881 and 5,809,796 sRNAs were obtained, and 280 and 306 miRNAs were identified from “Zifengyu” and “Dafugui”, respectively. A total of 237 conserved and 7 novel sequences of miRNAs were differentially expressed between the two cultivars, and we predicted and annotated their potential target genes. Subsequently, 7 differentially expressed candidate miRNAs were screened according to their target genes annotated in KEGG pathways, and the expression patterns of miRNAs and corresponding target genes were elucidated. We found that miR5254, miR165a-3p, miR3897-3p and miR6450a might be involved in the P. lactiflora response to B. cinerea infection. These results provide insight into the molecular mechanisms responsible for resistance to B. cinerea in P. lactiflora. Full article
(This article belongs to the Section Population and Evolutionary Genetics and Genomics)
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Open AccessArticle
Identification of 4CL Genes in Desert Poplars and Their Changes in Expression in Response to Salt Stress
Genes 2015, 6(3), 901-917; https://doi.org/10.3390/genes6030901 - 18 Sep 2015
Cited by 9 | Viewed by 1931
Abstract
4-Coumarate:CoA ligase (4CL) genes are critical for the biosynthesis of plant phenylpropanoids. Here we identified 20 4CL genes in the genomes of two desert poplars (Populus euphratica and P. pruinosa) and salt-sensitive congener (P. trichocarpa), [...] Read more.
4-Coumarate:CoA ligase (4CL) genes are critical for the biosynthesis of plant phenylpropanoids. Here we identified 20 4CL genes in the genomes of two desert poplars (Populus euphratica and P. pruinosa) and salt-sensitive congener (P. trichocarpa), but 12 in Salix suchowensis (Salix willow). Phylogenetic analyses clustered all Salicaceae 4CL genes into two clades, and one of them (corresponding to the 4CL-like clade from Arabidopsis) showed signals of adaptive evolution, with more genes retained in Populus than Salix and Arabidopsis. We also found that 4CL12 (in 4CL-like clade) showed positive selection along the two desert poplar lineages. Transcriptional profiling analyses indicated that the expression of 4CL2, 4CL11, and 4CL12 changed significantly in one or both desert poplars in response to salt stress compared to that of in P. trichocarpa. Our results suggest that the evolution of the 4CL genes may have contributed to the development of salt tolerance in the two desert poplars. Full article
(This article belongs to the Section Population and Evolutionary Genetics and Genomics)
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Open AccessArticle
Heterogeneous DNA Methylation Patterns in the GSTP1 Promoter Lead to Discordant Results between Assay Technologies and Impede Its Implementation as Epigenetic Biomarkers in Breast Cancer
Genes 2015, 6(3), 878-900; https://doi.org/10.3390/genes6030878 - 17 Sep 2015
Cited by 7 | Viewed by 2239
Abstract
Altered DNA methylation patterns are found in many diseases, particularly in cancer, where the analysis of DNA methylation holds the promise to provide diagnostic, prognostic and predictive information of great clinical value. Methylation of the promoter-associated CpG island of GSTP1 occurs in many [...] Read more.
Altered DNA methylation patterns are found in many diseases, particularly in cancer, where the analysis of DNA methylation holds the promise to provide diagnostic, prognostic and predictive information of great clinical value. Methylation of the promoter-associated CpG island of GSTP1 occurs in many hormone-sensitive cancers, has been shown to be a biomarker for the early detection of cancerous lesions and has been associated with important clinical parameters, such as survival and response to treatment. In the current manuscript, we assessed the performance of several widely-used sodium bisulfite conversion-dependent methods (methylation-specific PCR, MethyLight, pyrosequencing and MALDI mass-spectrometry) for the analysis of DNA methylation patterns in the GSTP1 promoter. We observed large discordances between the results obtained by the different technologies. Cloning and sequencing of the investigated region resolved single-molecule DNA methylation patterns and identified heterogeneous DNA methylation patterns as the underlying cause of the differences. Heterogeneous DNA methylation patterns in the GSTP1 promoter constitute a major obstacle to the implementation of DNA methylation-based analysis of GSTP1 and might explain some of the contradictory findings in the analysis of the significance of GSTP1 promoter methylation in breast cancer. Full article
(This article belongs to the Special Issue Epigenetic Biomarkers)
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Open AccessReview
Replication Stress: A Lifetime of Epigenetic Change
Genes 2015, 6(3), 858-877; https://doi.org/10.3390/genes6030858 - 11 Sep 2015
Cited by 19 | Viewed by 3385
Abstract
DNA replication is essential for cell division. Challenges to the progression of DNA polymerase can result in replication stress, promoting the stalling and ultimately collapse of replication forks. The latter involves the formation of DNA double-strand breaks (DSBs) and has been linked to [...] Read more.
DNA replication is essential for cell division. Challenges to the progression of DNA polymerase can result in replication stress, promoting the stalling and ultimately collapse of replication forks. The latter involves the formation of DNA double-strand breaks (DSBs) and has been linked to both genome instability and irreversible cell cycle arrest (senescence). Recent technological advances have elucidated many of the factors that contribute to the sensing and repair of stalled or broken replication forks. In addition to bona fide repair factors, these efforts highlight a range of chromatin-associated changes at and near sites of replication stress, suggesting defects in epigenome maintenance as a potential outcome of aberrant DNA replication. Here, we will summarize recent insight into replication stress-induced chromatin-reorganization and will speculate on possible adverse effects for gene expression, nuclear integrity and, ultimately, cell function. Full article
(This article belongs to the Special Issue Chromatin Dynamics)
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Open AccessReview
Ecology and Evolution of the Human Microbiota: Fire, Farming and Antibiotics
Genes 2015, 6(3), 841-857; https://doi.org/10.3390/genes6030841 - 08 Sep 2015
Cited by 27 | Viewed by 4493
Abstract
Human activities significantly affect all ecosystems on the planet, including the assemblages that comprise our own microbiota. Over the last five million years, various evolutionary and ecological drivers have altered the composition of the human microbiota, including the use of fire, the invention [...] Read more.
Human activities significantly affect all ecosystems on the planet, including the assemblages that comprise our own microbiota. Over the last five million years, various evolutionary and ecological drivers have altered the composition of the human microbiota, including the use of fire, the invention of agriculture, and the increasing availability of processed foods after the Industrial Revolution. However, no factor has had a faster or more direct effect than antimicrobial agents. Biocides, disinfectants and antibiotics select for individual cells that carry resistance genes, immediately reducing both overall microbial diversity and within-species genetic diversity. Treated individuals may never recover their original diversity, and repeated treatments lead to a series of genetic bottlenecks. The sequential introduction of diverse antimicrobial agents has selected for increasingly complex DNA elements that carry multiple resistance genes, and has fostered their spread through the human microbiota. Practices that interfere with microbial colonization, such as sanitation, Caesarian births and bottle-feeding, exacerbate the effects of antimicrobials, generating species-poor and less resilient microbial assemblages in the developed world. More and more evidence is accumulating that these perturbations to our internal ecosystems lie at the heart of many diseases whose frequency has shown a dramatic increase over the last half century. Full article
(This article belongs to the Special Issue Antibiotic Resistance: Mobility and Microbiomes)
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Open AccessArticle
Epigenetic Heterogeneity of B-Cell Lymphoma: DNA Methylation, Gene Expression and Chromatin States
Genes 2015, 6(3), 812-840; https://doi.org/10.3390/genes6030812 - 07 Sep 2015
Cited by 14 | Viewed by 4725
Abstract
Mature B-cell lymphoma is a clinically and biologically highly diverse disease. Its diagnosis and prognosis is a challenge due to its molecular heterogeneity and diverse regimes of biological dysfunctions, which are partly driven by epigenetic mechanisms. We here present an integrative analysis of [...] Read more.
Mature B-cell lymphoma is a clinically and biologically highly diverse disease. Its diagnosis and prognosis is a challenge due to its molecular heterogeneity and diverse regimes of biological dysfunctions, which are partly driven by epigenetic mechanisms. We here present an integrative analysis of DNA methylation and gene expression data of several lymphoma subtypes. Our study confirms previous results about the role of stemness genes during development and maturation of B-cells and their dysfunction in lymphoma locking in more proliferative or immune-reactive states referring to B-cell functionalities in the dark and light zone of the germinal center and also in plasma cells. These dysfunctions are governed by widespread epigenetic effects altering the promoter methylation of the involved genes, their activity status as moderated by histone modifications and also by chromatin remodeling. We identified four groups of genes showing characteristic expression and methylation signatures among Burkitt’s lymphoma, diffuse large B cell lymphoma, follicular lymphoma and multiple myeloma. These signatures are associated with epigenetic effects such as remodeling from transcriptionally inactive into active chromatin states, differential promoter methylation and the enrichment of targets of transcription factors such as EZH2 and SUZ12. Full article
(This article belongs to the Special Issue Chromatin Dynamics)
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Open AccessReview
Chromatin Insulators and Topological Domains: Adding New Dimensions to 3D Genome Architecture
Genes 2015, 6(3), 790-811; https://doi.org/10.3390/genes6030790 - 01 Sep 2015
Cited by 7 | Viewed by 4370
Abstract
The spatial organization of metazoan genomes has a direct influence on fundamental nuclear processes that include transcription, replication, and DNA repair. It is imperative to understand the mechanisms that shape the 3D organization of the eukaryotic genomes. Chromatin insulators have emerged as one [...] Read more.
The spatial organization of metazoan genomes has a direct influence on fundamental nuclear processes that include transcription, replication, and DNA repair. It is imperative to understand the mechanisms that shape the 3D organization of the eukaryotic genomes. Chromatin insulators have emerged as one of the central components of the genome organization tool-kit across species. Recent advancements in chromatin conformation capture technologies have provided important insights into the architectural role of insulators in genomic structuring. Insulators are involved in 3D genome organization at multiple spatial scales and are important for dynamic reorganization of chromatin structure during reprogramming and differentiation. In this review, we will discuss the classical view and our renewed understanding of insulators as global genome organizers. We will also discuss the plasticity of chromatin structure and its re-organization during pluripotency and differentiation and in situations of cellular stress. Full article
(This article belongs to the Special Issue Chromatin Dynamics)
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Open AccessArticle
Genotype-Epigenotype Interaction at the IGF2 DMR
Genes 2015, 6(3), 777-789; https://doi.org/10.3390/genes6030777 - 28 Aug 2015
Viewed by 3066
Abstract
Paternally expressed Insulin-like Growth Factor II (IGF2) encodes a gene whose protein product functions as a potent growth mitogen. Overexpression of IGF2 has been implicated in a wide number of disorders and diseases. IGF2 is regulated in part by differential methylation of the [...] Read more.
Paternally expressed Insulin-like Growth Factor II (IGF2) encodes a gene whose protein product functions as a potent growth mitogen. Overexpression of IGF2 has been implicated in a wide number of disorders and diseases. IGF2 is regulated in part by differential methylation of the two parentally derived alleles. The differentially methylated region (DMR) located upstream of the imprinted promoters of IGF2 exhibits plasticity under environmental stress and is hypomethylated in several types of cancer. Through bisulfite pyrosequencing and confirmation by nucleotide sequencing, we discovered a CpG to CpC transversion that results in hypomethylation of one of the three CpGs comprising this DMR. The presence of the polymorphism introduces a genetic rather than an environmentally-driven epigenetic source of hypomethylation that is additive to non-genetic sources. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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Open AccessReview
Chromatin Dynamics in Vivo: A Game of Musical Chairs
Genes 2015, 6(3), 751-776; https://doi.org/10.3390/genes6030751 - 07 Aug 2015
Cited by 20 | Viewed by 3669
Abstract
Histones are a major component of chromatin, the nucleoprotein complex fundamental to regulating transcription, facilitating cell division, and maintaining genome integrity in almost all eukaryotes. In addition to canonical, replication-dependent histones, replication-independent histone variants exist in most eukaryotes. In recent years, steady progress [...] Read more.
Histones are a major component of chromatin, the nucleoprotein complex fundamental to regulating transcription, facilitating cell division, and maintaining genome integrity in almost all eukaryotes. In addition to canonical, replication-dependent histones, replication-independent histone variants exist in most eukaryotes. In recent years, steady progress has been made in understanding how histone variants assemble, their involvement in development, mitosis, transcription, and genome repair. In this review, we will focus on the localization of the major histone variants H3.3, CENP-A, H2A.Z, and macroH2A, as well as how these variants have evolved, their structural differences, and their functional significance in vivo. Full article
(This article belongs to the Special Issue Chromatin Dynamics)
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Open AccessReview
Contribution of Topological Domains and Loop Formation to 3D Chromatin Organization
Genes 2015, 6(3), 734-750; https://doi.org/10.3390/genes6030734 - 27 Jul 2015
Cited by 25 | Viewed by 5482
Abstract
Recent investigations on 3D chromatin folding revealed that the eukaryote genomes are both highly compartmentalized and extremely dynamic. This review presents the most recent advances in topological domains’ organization of the eukaryote genomes and discusses the relationship to chromatin loop formation. CTCF protein [...] Read more.
Recent investigations on 3D chromatin folding revealed that the eukaryote genomes are both highly compartmentalized and extremely dynamic. This review presents the most recent advances in topological domains’ organization of the eukaryote genomes and discusses the relationship to chromatin loop formation. CTCF protein appears as a central factor of these two organization levels having either a strong insulating role at TAD borders, or a weaker architectural role in chromatin loop formation. TAD borders directly impact on chromatin dynamics by restricting contacts within specific genomic portions thus confining chromatin loop formation within TADs. We discuss how sub-TAD chromatin dynamics, constrained into a recently described statistical helix conformation, can produce functional interactions by contact stabilization. Full article
(This article belongs to the Special Issue Chromatin Dynamics)
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Open AccessArticle
Full Genome Sequence Analysis of Two Isolates Reveals a Novel Xanthomonas Species Close to the Sugarcane Pathogen Xanthomonas albilineans
Genes 2015, 6(3), 714-733; https://doi.org/10.3390/genes6030714 - 23 Jul 2015
Cited by 5 | Viewed by 2449
Abstract
Xanthomonas albilineans is the bacterium responsible for leaf scald, a lethal disease of sugarcane. Within the Xanthomonas genus, X. albilineans exhibits distinctive genomic characteristics including the presence of significant genome erosion, a non-ribosomal peptide synthesis (NRPS) locus involved in albicidin biosynthesis, and a [...] Read more.
Xanthomonas albilineans is the bacterium responsible for leaf scald, a lethal disease of sugarcane. Within the Xanthomonas genus, X. albilineans exhibits distinctive genomic characteristics including the presence of significant genome erosion, a non-ribosomal peptide synthesis (NRPS) locus involved in albicidin biosynthesis, and a type 3 secretion system (T3SS) of the Salmonella pathogenicity island-1 (SPI-1) family. We sequenced two X. albilineans-like strains isolated from unusual environments, i.e., from dew droplets on sugarcane leaves and from the wild grass Paspalum dilatatum, and compared these genomes sequences with those of two strains of X. albilineans and three of Xanthomonas sacchari. Average nucleotide identity (ANI) and multi-locus sequence analysis (MLSA) showed that both X. albilineans-like strains belong to a new species close to X. albilineans that we have named “Xanthomonas pseudalbilineans. X. albilineans and “X. pseudalbilineans” share many genomic features including (i) the lack of genes encoding a hypersensitive response and pathogenicity type 3 secretion system (Hrp-T3SS), and (ii) genome erosion that probably occurred in a common progenitor of both species. Our comparative analyses also revealed specific genomic features that may help X. albilineans interact with sugarcane, e.g., a PglA endoglucanase, three TonB-dependent transporters and a glycogen metabolism gene cluster. Other specific genomic features found in the “X. pseudalbilineans” genome may contribute to its fitness and specific ecological niche. Full article
(This article belongs to the Section Population and Evolutionary Genetics and Genomics)
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Open AccessReview
The Structural Determinants behind the Epigenetic Role of Histone Variants
Genes 2015, 6(3), 685-713; https://doi.org/10.3390/genes6030685 - 23 Jul 2015
Cited by 18 | Viewed by 3109
Abstract
Histone variants are an important part of the histone contribution to chromatin epigenetics. In this review, we describe how the known structural differences of these variants from their canonical histone counterparts impart a chromatin signature ultimately responsible for their epigenetic contribution. In terms [...] Read more.
Histone variants are an important part of the histone contribution to chromatin epigenetics. In this review, we describe how the known structural differences of these variants from their canonical histone counterparts impart a chromatin signature ultimately responsible for their epigenetic contribution. In terms of the core histones, H2A histone variants are major players while H3 variant CenH3, with a controversial role in the nucleosome conformation, remains the genuine epigenetic histone variant. Linker histone variants (histone H1 family) haven’t often been studied for their role in epigenetics. However, the micro-heterogeneity of the somatic canonical forms of linker histones appears to play an important role in maintaining the cell-differentiated states, while the cell cycle independent linker histone variants are involved in development. A picture starts to emerge in which histone H2A variants, in addition to their individual specific contributions to the nucleosome structure and dynamics, globally impair the accessibility of linker histones to defined chromatin locations and may have important consequences for determining different states of chromatin metabolism. Full article
(This article belongs to the Special Issue Chromatin Dynamics)
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Open AccessArticle
Complete Genomic Characterization of Porcine Reproductive and Respiratory Syndrome Virus Strain HB-XL
Genes 2015, 6(3), 672-684; https://doi.org/10.3390/genes6030672 - 23 Jul 2015
Cited by 3 | Viewed by 2431
Abstract
Porcine reproductive and respiratory syndrome virus (PRRSV) is the causal agent of a serious disease of swine. Here, we report the genome sequence of PRRSV strain HB-XL isolated from a pig farm with a clinical outbreak of porcine reproductive and respiratory syndrome. The [...] Read more.
Porcine reproductive and respiratory syndrome virus (PRRSV) is the causal agent of a serious disease of swine. Here, we report the genome sequence of PRRSV strain HB-XL isolated from a pig farm with a clinical outbreak of porcine reproductive and respiratory syndrome. The genome is 15,323 bp long and has nine open reading frames (GenBank: KP162169). Comparative and phylogenetic analysis showed that HB-XL belongs to the highly pathogenic PRRSV (HP-PRRSV) subfamily in the family PRRSV. The viral nonstructural protein 2 (Nsp2) of the HB-XL strain contained 30 discontinuous amino acid (AA) deletions relative to that of the Nsp2 of the VR2332 strain. The AA substitutions R13 and R151 suggested high virulence of the HB-XL strain. The unique mutations in glycoprotein 5 (GP5) and Nsp2 revealed that HB-XL might be a novel variant PRRSV strain recombined with vaccine strains. However, the low morbidity and mortality in the pig herd from which HB-XL was isolated indicate that the virulence of the virus was weak, so it has potential as a future vaccine strain. Full article
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Open AccessArticle
Adaptive Evolution of CENP-A in Percid Fishes
Genes 2015, 6(3), 662-671; https://doi.org/10.3390/genes6030662 - 17 Jul 2015
Cited by 4 | Viewed by 1649
Abstract
Centromeric protein A (CENP-A) is the epigenetic determinant of centromeres. This protein has been shown to be adaptively evolving in a number of animal and plant species. In a previous communication we were able to demonstrate that signs of adaptive evolution were detected [...] Read more.
Centromeric protein A (CENP-A) is the epigenetic determinant of centromeres. This protein has been shown to be adaptively evolving in a number of animal and plant species. In a previous communication we were able to demonstrate that signs of adaptive evolution were detected in the comparison of CENP-A sequences from three percid fish species. In this study we isolated the CENP-A gene from eight additional species from the Percidae family. With these sequences and those previously obtained, we carried out a more robust statistical analysis of codon specific positive selection in CENP-A coding sequences of eleven percid species. We were able to demonstrate that at least two amino acid positions within the N-terminal tail are under strong positive selection and that one of these positions is potentially a substrate for phosphorylation. While nonsynonymous substitutions were detected in the histone fold domain, these were not statistically supported as resulting from positive selection. Full article
(This article belongs to the Section Population and Evolutionary Genetics and Genomics)
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Open AccessReview
Chromatin Dynamics in Lineage Commitment and Cellular Reprogramming
Genes 2015, 6(3), 641-661; https://doi.org/10.3390/genes6030641 - 17 Jul 2015
Cited by 7 | Viewed by 3658
Abstract
Dynamic structural properties of chromatin play an essential role in defining cell identity and function. Transcription factors and chromatin modifiers establish and maintain cell states through alteration of DNA accessibility and histone modifications. This activity is focused at both gene-proximal promoter regions and [...] Read more.
Dynamic structural properties of chromatin play an essential role in defining cell identity and function. Transcription factors and chromatin modifiers establish and maintain cell states through alteration of DNA accessibility and histone modifications. This activity is focused at both gene-proximal promoter regions and distally located regulatory elements. In the three-dimensional space of the nucleus, distal elements are localized in close physical proximity to the gene-proximal regulatory sequences through the formation of chromatin loops. These looping features in the genome are highly dynamic as embryonic stem cells differentiate and commit to specific lineages, and throughout reprogramming as differentiated cells reacquire pluripotency. Identifying these functional distal regulatory regions in the genome provides insight into the regulatory processes governing early mammalian development and guidance for improving the protocols that generate induced pluripotent cells. Full article
(This article belongs to the Special Issue Chromatin Dynamics)
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Open AccessArticle
Identification and Expression Analysis of PIN-Like (PILS) Gene Family of Rice Treated with Auxin and Cytokinin
Genes 2015, 6(3), 622-640; https://doi.org/10.3390/genes6030622 - 16 Jul 2015
Cited by 13 | Viewed by 3217
Abstract
The phytohormone auxin is one of the most important signaling molecules that undergo accumulation or depletion in a temporal or spatial manner due to wide arrays of changes in developmental or stress programs. Proper distribution, maintenance and homeostasis of auxin molecules across the [...] Read more.
The phytohormone auxin is one of the most important signaling molecules that undergo accumulation or depletion in a temporal or spatial manner due to wide arrays of changes in developmental or stress programs. Proper distribution, maintenance and homeostasis of auxin molecules across the plant systems are one of the most important phenomena required for proper growth and development of plant. The distribution and homeostasis of auxin is maintained by auxin transport systems across the plant. The auxin transportation is carried out by auxin transporter family proteins, popularly known as auxin efflux carriers (PINs). In this study, a sub-family of auxin efflux carrier (OsPILS) genes was identified from Oryza sativa and relative expression profile was studied by treating them with auxin and cytokinin. Oryza sativa encodes seven putative sub-cellularly localized transmembrane OsPILS genes distributed in five chromosomes. Differential expression of OsPILS genes was found to be modulated by auxin and cytokinin treatment. In auxin treated plants, all OsPILS genes were up-regulated in leaves and down regulated in roots during the third week time period of developmental stages. In the cytokinin treated plants, the maximum of OsPILS genes were up-regulated during the third week time period in root and leaf tissue. Regulation of gene expression of OsPILS genes by auxin and cytokinin during the third week time period revealed its important role in plant growth and development. Full article
(This article belongs to the Section Population and Evolutionary Genetics and Genomics)
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Open AccessReview
Nucleosome Dancing at the Tempo of Histone Tail Acetylation
Genes 2015, 6(3), 607-621; https://doi.org/10.3390/genes6030607 - 15 Jul 2015
Cited by 16 | Viewed by 2587
Abstract
The impact of histone acetylation on transcription was revealed over 50 years ago by Allfrey and colleagues. However, it took decades for an understanding of the fine mechanism by which this posttranslational modification affects chromatin structure and promotes transcription. Here, we review breakthroughs [...] Read more.
The impact of histone acetylation on transcription was revealed over 50 years ago by Allfrey and colleagues. However, it took decades for an understanding of the fine mechanism by which this posttranslational modification affects chromatin structure and promotes transcription. Here, we review breakthroughs linking histone tail acetylation, histone dynamics, and transcription. We also discuss the histone exchange during transcription and highlight the important function of a pool of non-chromatinized histones in chromatin dynamics. Full article
(This article belongs to the Special Issue Chromatin Dynamics)
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Open AccessReview
RNF20-SNF2H Pathway of Chromatin Relaxation in DNA Double-Strand Break Repair
Genes 2015, 6(3), 592-606; https://doi.org/10.3390/genes6030592 - 14 Jul 2015
Cited by 7 | Viewed by 3448
Abstract
Rapid progress in the study on the association of histone modifications with chromatin remodeling factors has broadened our understanding of chromatin dynamics in DNA transactions. In DNA double-strand break (DSB) repair, the well-known mark of histones is the phosphorylation of the H2A variant, [...] Read more.
Rapid progress in the study on the association of histone modifications with chromatin remodeling factors has broadened our understanding of chromatin dynamics in DNA transactions. In DNA double-strand break (DSB) repair, the well-known mark of histones is the phosphorylation of the H2A variant, H2AX, which has been used as a surrogate marker of DSBs. The ubiquitylation of histone H2B by RNF20 E3 ligase was recently found to be a DNA damage-induced histone modification. This modification is required for DSB repair and regulated by a distinctive pathway from that of histone H2AX phosphorylation. Moreover, the connection between H2B ubiquitylation and the chromatin remodeling activity of SNF2H has been elucidated. In this review, we summarize the current knowledge of RNF20-mediated processes and the molecular link to H2AX-mediated processes during DSB repair. Full article
(This article belongs to the Special Issue Chromatin Dynamics)
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Open AccessArticle
Alu Elements as Novel Regulators of Gene Expression in Type 1 Diabetes Susceptibility Genes?
Genes 2015, 6(3), 577-591; https://doi.org/10.3390/genes6030577 - 13 Jul 2015
Cited by 4 | Viewed by 2005
Abstract
Despite numerous studies implicating Alu repeat elements in various diseases, there is sparse information available with respect to the potential functional and biological roles of the repeat elements in Type 1 diabetes (T1D). Therefore, we performed a genome-wide sequence analysis of T1D candidate [...] Read more.
Despite numerous studies implicating Alu repeat elements in various diseases, there is sparse information available with respect to the potential functional and biological roles of the repeat elements in Type 1 diabetes (T1D). Therefore, we performed a genome-wide sequence analysis of T1D candidate genes to identify embedded Alu elements within these genes. We observed significant enrichment of Alu elements within the T1D genes (p-value < 10e−16), which highlights their importance in T1D. Functional annotation of T1D genes harboring Alus revealed significant enrichment for immune-mediated processes (p-value < 10e−6). We also identified eight T1D genes harboring inverted Alus (IRAlus) within their 3' untranslated regions (UTRs) that are known to regulate the expression of host mRNAs by generating double stranded RNA duplexes. Our in silico analysis predicted the formation of duplex structures by IRAlus within the 3'UTRs of T1D genes. We propose that IRAlus might be involved in regulating the expression levels of the host T1D genes. Full article
(This article belongs to the Special Issue Genetics of Diabetes)
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Open AccessArticle
Heritability and Genome-Wide Association Studies for Hair Color in a Dutch Twin Family Based Sample
Genes 2015, 6(3), 559-576; https://doi.org/10.3390/genes6030559 - 13 Jul 2015
Cited by 14 | Viewed by 2555
Abstract
Hair color is one of the most visible and heritable traits in humans. Here, we estimated heritability by structural equation modeling (N = 20,142), and performed a genome wide association (GWA) analysis (N = 7091) and a GCTA study (N = 3340) on [...] Read more.
Hair color is one of the most visible and heritable traits in humans. Here, we estimated heritability by structural equation modeling (N = 20,142), and performed a genome wide association (GWA) analysis (N = 7091) and a GCTA study (N = 3340) on hair color within a large cohort of twins, their parents and siblings from the Netherlands Twin Register (NTR). Self-reported hair color was analyzed as five binary phenotypes, namely “blond versus non-blond”, “red versus non-red”, “brown versus non-brown”, “black versus non-black”, and “light versus dark”. The broad-sense heritability of hair color was estimated between 73% and 99% and the genetic component included non-additive genetic variance. Assortative mating for hair color was significant, except for red and black hair color. From GCTA analyses, at most 24.6% of the additive genetic variance in hair color was explained by 1000G well-imputed SNPs. Genome-wide association analysis for each hair color showed that SNPs in the MC1R region were significantly associated with red, brown and black hair, and also with light versus dark hair color. Five other known genes (HERC2, TPCN2, SLC24A4, IRF4, and KITLG) gave genome-wide significant hits for blond, brown and light versus dark hair color. We did not find and replicate any new loci for hair color. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
Open AccessReview
Chromatin Dynamics in the Regulation of CFTR Expression
Genes 2015, 6(3), 543-558; https://doi.org/10.3390/genes6030543 - 13 Jul 2015
Cited by 12 | Viewed by 2364
Abstract
The contribution of chromatin dynamics to the regulation of human disease-associated loci such as the cystic fibrosis transmembrane conductance regulator (CFTR) gene has been the focus of intensive experimentation for many years. Recent technological advances in the analysis of transcriptional mechanisms [...] Read more.
The contribution of chromatin dynamics to the regulation of human disease-associated loci such as the cystic fibrosis transmembrane conductance regulator (CFTR) gene has been the focus of intensive experimentation for many years. Recent technological advances in the analysis of transcriptional mechanisms across the entire human genome have greatly facilitated these studies. In this review we describe the complex machinery of tissue-specific regulation of CFTR expression, and put earlier observations in context by incorporating them into datasets generated by the most recent genomics methods. Though the gene promoter is required for CFTR expression, cell-type specific regulatory elements are located elsewhere in the gene and in flanking intergenic regions. Probably within its own topological domain established by the architectural proteins CTCF and cohesin, the CFTR locus utilizes chromatin dynamics to remodel nucleosomes, recruit cell-selective transcription factors, and activate intronic enhancers. These cis-acting elements are then brought to the gene promoter by chromatin looping mechanisms, which establish long-range interactions across the locus. Despite its complexity, the CFTR locus provides a paradigm for elucidating the critical role of chromatin dynamics in the transcription of individual human genes. Full article
(This article belongs to the Special Issue Chromatin Dynamics)
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Open AccessReview
One, Two, Three: Polycomb Proteins Hit All Dimensions of Gene Regulation
Genes 2015, 6(3), 520-542; https://doi.org/10.3390/genes6030520 - 10 Jul 2015
Cited by 10 | Viewed by 3534
Abstract
Polycomb group (PcG) proteins contribute to the formation and maintenance of a specific repressive chromatin state that prevents the expression of genes in a particular space and time. Polycomb repressive complexes (PRCs) consist of several PcG proteins with specific regulatory or catalytic properties. [...] Read more.
Polycomb group (PcG) proteins contribute to the formation and maintenance of a specific repressive chromatin state that prevents the expression of genes in a particular space and time. Polycomb repressive complexes (PRCs) consist of several PcG proteins with specific regulatory or catalytic properties. PRCs are recruited to thousands of target genes, and various recruitment factors, including DNA-binding proteins and non-coding RNAs, are involved in the targeting. PcG proteins contribute to a multitude of biological processes by altering chromatin features at different scales. PcG proteins mediate both biochemical modifications of histone tails and biophysical modifications (e.g., chromatin fiber compaction and three-dimensional (3D) chromatin conformation). Here, we review the role of PcG proteins in nuclear architecture, describing their impact on the structure of the chromatin fiber, on chromatin interactions, and on the spatial organization of the genome in nuclei. Although little is known about the role of plant PcG proteins in nuclear organization, much is known in the animal field, and we highlight similarities and differences in the roles of PcG proteins in 3D gene regulation in plants and animals. Full article
(This article belongs to the Special Issue Chromatin Dynamics)
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Open AccessArticle
Relation between ADIPOQ Gene Polymorphisms and Type 2 Diabetes
Genes 2015, 6(3), 512-519; https://doi.org/10.3390/genes6030512 - 08 Jul 2015
Cited by 9 | Viewed by 2246
Abstract
Objective: The manuscript investigates the relation between adiponectin gene (ADIPOQ) polymorphisms and type 2 diabetes mellitus (T2DM) in a Chinese population. Methods: We designed a case-control study involving 340 normal glucose tolerant (NGT) subjects and 340 type 2 diabetes patients. Three [...] Read more.
Objective: The manuscript investigates the relation between adiponectin gene (ADIPOQ) polymorphisms and type 2 diabetes mellitus (T2DM) in a Chinese population. Methods: We designed a case-control study involving 340 normal glucose tolerant (NGT) subjects and 340 type 2 diabetes patients. Three SNPs (rs182052, rs1501299, and rs7627128) were genotyped by TaqMan methods. Results: We found that rs7627128, rs1501299 and rs182052 were significantly associated with T2DM. Haplotypes analysis indicated that the frequency of the haplotypes A-A-T was frequent in T2DM patients (OR = 2.10; 95%CI: 1.44–2.90; p < 0.001), but G-A-T was more frequent in the control group than in the T2DM group (OR = 0.66; 95%CI: 0.54–0.81; p < 0.001). Conclusion: The ADIPOQ genetic polymorphisms were associated with type 2 diabetes in a Chinese population. Full article
Open AccessReview
Hedgehog Signaling in Malignant Pleural Mesothelioma
Genes 2015, 6(3), 500-511; https://doi.org/10.3390/genes6030500 - 08 Jul 2015
Cited by 6 | Viewed by 2823
Abstract
Malignant pleural mesothelioma (MPM) is a cancer associated with exposure to asbestos fibers, which accumulate in the pleural space, damage tissue and stimulate regeneration. Hedgehog signaling is a pathway important during embryonic mesothelium development and is inactivated in adult mesothelium. The pathway is [...] Read more.
Malignant pleural mesothelioma (MPM) is a cancer associated with exposure to asbestos fibers, which accumulate in the pleural space, damage tissue and stimulate regeneration. Hedgehog signaling is a pathway important during embryonic mesothelium development and is inactivated in adult mesothelium. The pathway is reactivated in some MPM patients with poor clinical outcome, mainly mediated by the expression of the ligands. Nevertheless, mutations in components of the pathway have been observed in a few cases. Data from different MPM animal models and primary culture suggest that both autocrine and paracrine Hedgehog signaling are important to maintain tumor growth. Drugs inhibiting the pathway at the level of the smoothened receptor (Smo) or glioma-associated protein transcription factors (Gli) have been used mostly in experimental models. For clinical development, biomarkers are necessary for the selection of patients who can benefit from Hedgehog signaling inhibition. Full article
(This article belongs to the Special Issue Hedgehog Signaling Gene Regulatory Networks)
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Open AccessReview
Molecular and Cellular Mechanisms of Action of Tumour Suppressor GAS5 LncRNA
Genes 2015, 6(3), 484-499; https://doi.org/10.3390/genes6030484 - 07 Jul 2015
Cited by 97 | Viewed by 3651
Abstract
It is increasingly recognised that lncRNAs play essential regulatory roles in fundamental biological processes and, consequently, that their dysregulation may contribute to major human diseases, including cancer. Better understanding of lncRNA biology may therefore offer new insights into pathogenetic mechanisms and thereby offer [...] Read more.
It is increasingly recognised that lncRNAs play essential regulatory roles in fundamental biological processes and, consequently, that their dysregulation may contribute to major human diseases, including cancer. Better understanding of lncRNA biology may therefore offer new insights into pathogenetic mechanisms and thereby offer novel opportunities for diagnosis and therapy. Of particular interest in this regard is GAS5 lncRNA, which is down-regulated in multiple cancers, with expression levels related to both clinico-pathological characteristics and patient prognosis. Functional studies have further shown that GAS5 lncRNA both inhibits the proliferation and promotes the apoptosis of multiple cell types, and that together these cellular mechanisms of action are likely to form the basis of its tumour suppressor action. At the same time, advances have been made in our understanding of the molecular mechanisms of GAS5 lncRNA action in recent years, including riborepression of certain steroid hormone receptors and sequestration of miR-21, impacting key regulatory pathways of cell survival. Overall this accumulating knowledge has the potential to improve both the diagnosis and treatment of cancer, and ultimately patient outcome. Full article
(This article belongs to the Special Issue Long Noncoding RNAs)
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Open AccessReview
From Structural Variation of Gene Molecules to Chromatin Dynamics and Transcriptional Bursting
Genes 2015, 6(3), 469-483; https://doi.org/10.3390/genes6030469 - 30 Jun 2015
Cited by 4 | Viewed by 2376
Abstract
Transcriptional activation of eukaryotic genes is accompanied, in general, by a change in the sensitivity of promoter chromatin to endonucleases. The structural basis of this alteration has remained elusive for decades; but the change has been viewed as a transformation of one structure [...] Read more.
Transcriptional activation of eukaryotic genes is accompanied, in general, by a change in the sensitivity of promoter chromatin to endonucleases. The structural basis of this alteration has remained elusive for decades; but the change has been viewed as a transformation of one structure into another, from “closed” to “open” chromatin. In contradistinction to this static and deterministic view of the problem, a dynamical and probabilistic theory of promoter chromatin has emerged as its solution. This theory, which we review here, explains observed variation in promoter chromatin structure at the level of single gene molecules and provides a molecular basis for random bursting in transcription—the conjecture that promoters stochastically transition between transcriptionally conducive and inconducive states. The mechanism of transcriptional regulation may be understood only in probabilistic terms. Full article
(This article belongs to the Special Issue Chromatin Dynamics)
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Open AccessReview
Regulation of Unperturbed DNA Replication by Ubiquitylation
Genes 2015, 6(3), 451-468; https://doi.org/10.3390/genes6030451 - 25 Jun 2015
Cited by 8 | Viewed by 2562
Abstract
Posttranslational modification of proteins by means of attachment of a small globular protein ubiquitin (i.e., ubiquitylation) represents one of the most abundant and versatile mechanisms of protein regulation employed by eukaryotic cells. Ubiquitylation influences almost every cellular process and its key [...] Read more.
Posttranslational modification of proteins by means of attachment of a small globular protein ubiquitin (i.e., ubiquitylation) represents one of the most abundant and versatile mechanisms of protein regulation employed by eukaryotic cells. Ubiquitylation influences almost every cellular process and its key role in coordination of the DNA damage response is well established. In this review we focus, however, on the ways ubiquitylation controls the process of unperturbed DNA replication. We summarise the accumulated knowledge showing the leading role of ubiquitin driven protein degradation in setting up conditions favourable for replication origin licensing and S-phase entry. Importantly, we also present the emerging major role of ubiquitylation in coordination of the active DNA replication process: preventing re-replication, regulating the progression of DNA replication forks, chromatin re-establishment and disassembly of the replisome at the termination of replication forks. Full article
(This article belongs to the Special Issue DNA Replication)
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