Genes

1546 KiB

Open AccessReview

The Genetic Architecture of Type 1 Diabetes

by Samuel T Jerram and Richard David Leslie

Genes 2017, 8(8), 209; https://doi.org/10.3390/genes8080209 - 22 Aug 2017

Cited by 52 | Viewed by 11301

Type 1 diabetes (T1D) is classically characterised by the clinical need for insulin, the presence of disease-associated serum autoantibodies, and an onset in childhood. The disease, as with other autoimmune diseases, is due to the interaction of genetic and non-genetic effects, which induce [...] Read more.

Type 1 diabetes (T1D) is classically characterised by the clinical need for insulin, the presence of disease-associated serum autoantibodies, and an onset in childhood. The disease, as with other autoimmune diseases, is due to the interaction of genetic and non-genetic effects, which induce a destructive process damaging insulin-secreting cells. In this review, we focus on the nature of this interaction, and how our understanding of that gene–environment interaction has changed our understanding of the nature of the disease. We discuss the early onset of the disease, the development of distinct immunogenotypes, and the declining heritability with increasing age at diagnosis. Whilst Human Leukocyte Antigens (HLA) have a major role in causing T1D, we note that some of these HLA genes have a protective role, especially in children, whilst other non-HLA genes are also important. In adult-onset T1D, the disease is often not insulin-dependent at diagnosis, and has a dissimilar immunogenotype with reduced genetic predisposition. Finally, we discuss the putative nature of the non-genetic factors and how they might interact with genetic susceptibility, including preliminary studies of the epigenome associated with T1D. Full article

(This article belongs to the Special Issue Genetics and Functional Genomics of Diabetes Mellitus)

► Show Figures

Figure 1

2700 KiB

Open AccessArticle

A Rare Form of Retinal Dystrophy Caused by Hypomorphic Nonsense Mutations in CEP290

by Susanne Roosing, Frans P. M. Cremers, Frans C. C. Riemslag, Marijke N. Zonneveld-Vrieling, Herman E. Talsma, Francoise J. M. Klessens-Godfroy, Anneke I. Den Hollander and L. Ingeborgh Van den Born

Genes 2017, 8(8), 208; https://doi.org/10.3390/genes8080208 - 22 Aug 2017

Cited by 22 | Viewed by 5235

Abstract

Purpose: To identify the gene defect and to study the clinical characteristics and natural course of disease in a family originally diagnosed with oligocone trichromacy (OT), a rare congenital cone dysfunction syndrome. Methods: Extensive clinical and ophthalmologic assessment was performed on two siblings [...] Read more.

Purpose: To identify the gene defect and to study the clinical characteristics and natural course of disease in a family originally diagnosed with oligocone trichromacy (OT), a rare congenital cone dysfunction syndrome. Methods: Extensive clinical and ophthalmologic assessment was performed on two siblings with OT and long-term follow up data were analyzed. Subsequently, whole exome sequencing (WES) and Sanger sequence analysis of CEP290 was performed in the two siblings. Additionally, the identified CEP290 mutations were analyzed in persons with achromatopsia (ACHM) (n = 23) and autosomal recessive or isolated cone dystrophy (CD; n = 145). Results: In the first decade of life, the siblings were diagnosed with OT based on low visual acuity, photophobia, nystagmus, and absent cone response on electroretinography , but with normal color discrimination. Over time, the phenotype of OT evolved to a progressive degenerative disease without any CEP290-associated non-ocular features. In both siblings, two nonsense mutations (c.451C>T; p.(Arg151*) and c.4723A>T; p.(Lys1575*)) in CEP290 were found. Previously, p.(Arg151*) was demonstrated to induce nonsense-mediated alternative splicing events leading to intact open reading frames of the resulting mRNA products (p.(Leu148_Glu165del) and p.(Leu148_Lys172del)). mRNA analysis for p.(Lys1575*) confirmed a suspected hypomorphic character, as exon 36 skipping was observed in a small fraction of CEP290 mRNA, resulting in a 36 aa in-frame deletion (p.(Glu1569_Trp1604del)). No additional cases carrying these variants were identified in the ACHM and CD cohorts. Conclusions: Compound heterozygous hypomorphic mutations in CEP290 may lead to a rare form of cone-dominated retinal dystrophy, a novel phenotype belonging to the CEP290-associated spectrum of ciliopathies. These findings provide insight into the effect of CEP290 mutations on the clinical phenotype. Full article

(This article belongs to the Special Issue Inherited Retinal Disease: Novel Candidate Genes, Genotype–Phenotype Correlations and Inheritance Models)

► Show Figures

Figure 1

280 KiB

Open AccessReview

Long Noncoding RNAs as Diagnostic and Therapeutic Targets in Type 2 Diabetes and Related Complications

by Fatjon Leti and Johanna K. DiStefano

Genes 2017, 8(8), 207; https://doi.org/10.3390/genes8080207 - 22 Aug 2017

Cited by 70 | Viewed by 5696

Abstract

Protein-coding genes represent only a small fraction of the human genome. In the past, the majority of the genomic sequence has been considered transcriptionally silent, but recent large-scale studies have uncovered an array of functionally significant elements, including non-protein-coding transcripts, within these noncoding [...] Read more.

Protein-coding genes represent only a small fraction of the human genome. In the past, the majority of the genomic sequence has been considered transcriptionally silent, but recent large-scale studies have uncovered an array of functionally significant elements, including non-protein-coding transcripts, within these noncoding regions of the human genome. Long noncoding RNAs (lncRNAs), a class of noncoding transcripts with lengths >200 nucleotides, are pervasively transcribed in the genome and function as signals, decoys, guides, or scaffolds to regulate gene expression. More than 200 diseases have been associated with dysregulated or dysfunctional lncRNAs, and new associations continue to accumulate in the literature. The role of lncRNAs in the pathogenesis of type 2 diabetes mellitus and related complications has only recently been recognized, but there is already evidence for their involvement in many of the pathophysiological mechanisms underlying the disease. In this review, we summarize the current knowledge of the functions and underlying mechanisms of lncRNA activity with a focus on type 2 diabetes mellitus and related renal and retinal complications of the disease. We also discuss the potential of lncRNAs to serve as therapeutic targets for drug development and diagnostic markers for clinical applications in the management of diabetes. Full article

(This article belongs to the Special Issue Non-coding RNAs)

1681 KiB

Open AccessArticle

Viral Infection Identifies Micropeptides Differentially Regulated in smORF-Containing lncRNAs

by Brandon S. Razooky, Benedikt Obermayer, Joshua Biggs O’May and Alexander Tarakhovsky

Genes 2017, 8(8), 206; https://doi.org/10.3390/genes8080206 - 21 Aug 2017

Cited by 43 | Viewed by 6754

Abstract

Viral infection leads to a robust cellular response whereby the infected cell produces hundreds of molecular regulators to combat infection. Currently, non-canonical components, e.g., long noncoding RNAs (lncRNAs) have been added to the repertoire of immune regulators involved in the antiviral program. Interestingly, [...] Read more.

Viral infection leads to a robust cellular response whereby the infected cell produces hundreds of molecular regulators to combat infection. Currently, non-canonical components, e.g., long noncoding RNAs (lncRNAs) have been added to the repertoire of immune regulators involved in the antiviral program. Interestingly, studies utilizing next-generation sequencing technologies show that a subset of the >10,000 lncRNAs in the mammalian genome contain small open reading frames (smORFs) associated with active translation, i.e., many lncRNAs are not noncoding. Here, we use genome-wide high-throughput methods to identify potential micropeptides in smORF-containing lncRNAs involved in the immune response. Using influenza as a viral infection model, we performed RNA-seq and ribosome profiling to track expression and translation of putative lncRNAs that may encode for peptides and identify tens of potential candidates. Interestingly, many of these peptides are highly conserved at the protein level, strongly suggesting biological relevance and activity. By perusing publicly available data sets, four potential peptides of interest seem common to stress induction and/or are highly conserved; potential peptides from the MMP24-AS1, ZFAS1, RP11-622K12.1, and MIR22HG genes. Interestingly, using an antibody against the potential peptide encoded by MIR22HG RNA, we show that the peptide is stably expressed in the absence of infection, and upregulated in response to infection, corroborating the prediction of the ribosome profiling results. These data show the utility of perturbation approaches in identifying potentially relevant novel molecules encoded in the genome. Full article

(This article belongs to the Special Issue The Value of Being Different: Ultraconserved Genomic Elements, Micro Peptides and Chimeric RNAs)

► Show Figures

Figure 1

2305 KiB

Open AccessArticle

Mapping of QTLs for Seed Phorbol Esters, a Toxic Chemical in Jatropha curcas (L.)

by Kitiya Amkul, Kularb Laosatit, Prakit Somta, Sangrea Shim, Suk-Ha Lee, Patcharin Tanya and Peerasak Srinives

Genes 2017, 8(8), 205; https://doi.org/10.3390/genes8080205 - 18 Aug 2017

Cited by 11 | Viewed by 4697

Abstract

Jatropha (Jatropha curcas L.) is an oil-bearing plant that has potential to be cultivated as a biodiesel crop. The seed cake after oil extraction has 40–50% protein that can be used in animal feeds. A major limitation in utilizing the cake is [...] Read more.

Jatropha (Jatropha curcas L.) is an oil-bearing plant that has potential to be cultivated as a biodiesel crop. The seed cake after oil extraction has 40–50% protein that can be used in animal feeds. A major limitation in utilizing the cake is the presence of phorbol esters (PE), a heat-tolerant toxic chemical. To identify the quantitative trait loci (QTLs) for PE, we constructed a genetic linkage map from an F₂ population of 95 individuals from a cross “Chai Nat” × “M10” using 143 simple sequence repeat (SSR) markers. M10 is low in seed PE while Chai Nat is high. Seeds from each F₂ individual were quantified for PE content by high performance liquid chromatography. A single marker analysis revealed five markers from linkage group 3 (LG3) and nine markers from LG8 associated with seed PE. Inclusive composite interval mapping identified two QTLs, each on LG3 (qPE3.1) and LG8 (qPE8.1) responsible for the PE. qPE3.1 and qPE8.1 accounted for 14.10%, and 15.49% of total variation in seed PE, respectively. Alelle(s) from M10 at qPE3.1 increased seed PE, while at qPE8.1 decreased seed PE. qPE3.1 is a new loci for PE, while qPE8.1 is the same locus with that reported recently for PE. Full article

(This article belongs to the Special Issue Plant Genomics and Epigenomics for Trait Improvement)

► Show Figures

Figure 1

1353 KiB

Open AccessArticle

Variation in the Ovine KAP6-3 Gene (KRTAP6-3) Is Associated with Variation in Mean Fibre Diameter-Associated Wool Traits

by Shaobin Li, Huitong Zhou, Hua Gong, Fangfang Zhao, Jiqing Wang, Yuzhu Luo and Jon G. H. Hickford

Genes 2017, 8(8), 204; https://doi.org/10.3390/genes8080204 - 18 Aug 2017

Cited by 28 | Viewed by 3944

Abstract

Polymerase chain reaction-single stranded conformational polymorphism (PCR-SSCP) analysis was used to investigate variation in the ovine KAP6-3 gene (KRTAP6-3) in 383 Merino × Southdown-cross lambs from four sire-lines, and to determine whether this variation affects wool traits. Five PCR-SSCP banding patterns, [...] Read more.

Polymerase chain reaction-single stranded conformational polymorphism (PCR-SSCP) analysis was used to investigate variation in the ovine KAP6-3 gene (KRTAP6-3) in 383 Merino × Southdown-cross lambs from four sire-lines, and to determine whether this variation affects wool traits. Five PCR-SSCP banding patterns, representing five different nucleotide sequences, were detected, including four previously identified (named A, B, C, and F) variants and one newly identified (named G) variant. A new non-synonymous single nucleotide polymorphism (SNP) and a 45-bp deletion were detected in variant G. Of the three common genotypes (AA, AB, and AG) identified in these sheep, wool from sheep that were AG, on average, had a lower mean fibre diameter (MFD), fibre diameter standard deviation (FDSD), and prickle factor (PF) than wool from AA sheep, whereas wool from AB sheep, on average, had a higher MFD, FDSD, and PF than wool from AA sheep. This suggests that variation in ovine KRTAP6-3 affect MFD, FDSD, and PF, and that this gene may have potential for use as a gene-maker for improving fibre diameter-associated wool traits. Full article

(This article belongs to the Section Molecular Genetics and Genomics)

► Show Figures

Figure 1

2594 KiB

Open AccessArticle

Transcriptome Analysis Reveals Long Intergenic Noncoding RNAs Contributed to Growth and Meat Quality Differences between Yorkshire and Wannanhua Pig

by Cheng Zou, Sha Li, Lulu Deng, Yang Guan, Dake Chen, Xiongkun Yuan, Tianrui Xia, Xinglin He, Yawei Shan and Changchun Li

Genes 2017, 8(8), 203; https://doi.org/10.3390/genes8080203 - 18 Aug 2017

Cited by 25 | Viewed by 5284

Abstract

There are major differences between Yorkshire (lean-type) and Wannanhua pig (fat-type) in terms of growth performance and meat quality. Long intergenic noncoding RNAs (lincRNAs) are a class of regulators that are involved in numerous biological processes and widely identified in many species. However, [...] Read more.

There are major differences between Yorkshire (lean-type) and Wannanhua pig (fat-type) in terms of growth performance and meat quality. Long intergenic noncoding RNAs (lincRNAs) are a class of regulators that are involved in numerous biological processes and widely identified in many species. However, the role of lincRNAs in pig is largely unknown, and the mechanisms by which they affect growth and meat quality are elusive. In this study, we used published data to identify 759 lincRNAs in porcine longissimus dorsi muscle. These putative lincRNAs shared many features with mammalian lincRNAs, such as shorter length and fewer exons. Gene ontology and pathway analysis indicated that many potential target genes (PTGs) of lincRNAs were involved in muscle growth-related and meat quality-related biological processes. Moreover, we constructed a co-expression network between differentially expressed lincRNAs (DELs) and their PTGs, and found a potential mechanism that most DELs can use to upregulate their PTGs, which may finally contribute to the growth and meat quality differences between the two breeds through an unknown manner. This work details some lincRNAs and their PTGs related to muscle growth or meat quality, and facilitates future research on the roles of lincRNAs in these two types of pig, as well as molecular-assisted breeding for pig. Full article

► Show Figures

Figure 1

776 KiB

Open AccessArticle

Distribution of FMR1 and FMR2 Repeats in Argentinean Patients with Primary Ovarian Insufficiency

by Lucía Daniela Espeche, Violeta Chiauzzi, Ianina Ferder, Mehrnoosh Arrar, Andrea Paula Solari, Carlos David Bruque, Marisol Delea, Susana Belli, Cecilia Soledad Fernández, Noemí Delia Buzzalino, Eduardo Hernán Charreau and Liliana Beatriz Dain

Genes 2017, 8(8), 194; https://doi.org/10.3390/genes8080194 - 16 Aug 2017

Cited by 10 | Viewed by 4369

Abstract

The premutation state of FMR1 (Fragile X Mental Retardation 1) has been associated with primary ovarian insufficiency (POI), and is the most common known genetic cause for 46,XX patients. Nevertheless, very few studies have analyzed its frequency in Latin American populations. Additionally, a [...] Read more.

The premutation state of FMR1 (Fragile X Mental Retardation 1) has been associated with primary ovarian insufficiency (POI), and is the most common known genetic cause for 46,XX patients. Nevertheless, very few studies have analyzed its frequency in Latin American populations. Additionally, a relationship between alleles carrying a cryptic microdeletion in the 5’UTR of FMR2 and the onset of POI has only been studied in one population. Our aim was to analyze the incidence of FMR1 premutations and putative microdeletions in exon 1 of FMR2 in a cohort of Argentinean women with POI. We studied 133 patients and 84 controls. Fluorescent PCR was performed, and the FMR2 exon 1 was further sequenced in samples presenting less than 11 repeats. We found the frequency of FMR1 premutations to be 6.7% and 2.9% for familial and sporadic patients, respectively. Among controls, 1/84 women presented a premutation. In addition, although we did not find microdeletions in FMR2, we observed a change (T >C) adjacent to the repeats in two sisters with POI. Given the repetitive nature of the sequence involved, we could not ascertain whether this represents a single nucleotide polymorphism (SNP) or a deletion. Therefore, a relationship between FMR2 and POI could not be established for our population. Full article

(This article belongs to the Section Human Genomics and Genetic Diseases)

► Show Figures

Figure 1

578 KiB

Open AccessArticle

Mutation Clusters from Cancer Exome

by Zura Kakushadze and Willie Yu

Genes 2017, 8(8), 201; https://doi.org/10.3390/genes8080201 - 15 Aug 2017

Cited by 2 | Viewed by 46303

Abstract

We apply our statistically deterministic machine learning/clustering algorithm *K-means (recently developed in https://ssrn.com/abstract=2908286) to 10,656 published exome samples for 32 cancer types. A majority of cancer types exhibit a mutation clustering structure. Our results are in-sample stable. They are also out-of-sample stable [...] Read more.

We apply our statistically deterministic machine learning/clustering algorithm *K-means (recently developed in https://ssrn.com/abstract=2908286) to 10,656 published exome samples for 32 cancer types. A majority of cancer types exhibit a mutation clustering structure. Our results are in-sample stable. They are also out-of-sample stable when applied to 1389 published genome samples across 14 cancer types. In contrast, we find in- and out-of-sample instabilities in cancer signatures extracted from exome samples via nonnegative matrix factorization (NMF), a computationally-costly and non-deterministic method. Extracting stable mutation structures from exome data could have important implications for speed and cost, which are critical for early-stage cancer diagnostics, such as novel blood-test methods currently in development. Full article

(This article belongs to the Special Issue Integrative Genomics and Systems Medicine in Cancer)

► Show Figures

Figure 1

1818 KiB

Open AccessArticle

Large Introns of 5 to 10 Kilo Base Pairs Can Be Spliced out in Arabidopsis

by Ning Chang, Qingqing Sun, Jinglei Hu, Chuanjing An and And Hongbo Gao

Genes 2017, 8(8), 200; https://doi.org/10.3390/genes8080200 - 11 Aug 2017

Cited by 14 | Viewed by 5146

Abstract

Most of the eukaryotic genes contain introns, which are removed from the pre-RNA during RNA processing. In contrast to the introns in animals, which are usually several kilo base pairs (kb), those in plants generally are very small, which are mostly from dozens [...] Read more.

Most of the eukaryotic genes contain introns, which are removed from the pre-RNA during RNA processing. In contrast to the introns in animals, which are usually several kilo base pairs (kb), those in plants generally are very small, which are mostly from dozens of base pairs (bp) to a few hundred bp. According to annotation version 10.0 of the genome of Arabidopsis thaliana, there are 127,854 introns in the nuclear genes; 99.23% of them are less than 1 kb, and only 16 introns are annotated to be larger than 5 kb, which are extremely large introns (ELI) in Arabidopsis. To learn whether these introns are true introns or not and how large introns could be in Arabidopsis, RT-PCR analysis of genes containing these ELIs were carried out. The results indicated that some of these putative introns are indeed ELIs. These ELIs are mainly composed of transposons or transposable elements (TE), excepting one, whose counterparts are also very long in diverse plant species. Thus, this study confirms the existence of introns larger than 5 kb or even 10 kb in Arabidopsis. Full article

(This article belongs to the Section Plant Genetics and Genomics)

► Show Figures

Figure 1

5262 KiB

Open AccessArticle

Two C3H Type Zinc Finger Protein Genes, CpCZF1 and CpCZF2, from Chimonanthus praecox Affect Stamen Development in Arabidopsis

by Huamin Liu, Renwei Huang, Jing Ma, Shunzhao Sui, Yulong Guo, Daofeng Liu, Zhineng Li, Yechun Lin and Mingyang Li

Genes 2017, 8(8), 199; https://doi.org/10.3390/genes8080199 - 10 Aug 2017

Cited by 25 | Viewed by 5569

Abstract

Wintersweet (Chimonanthus praecox) is a popular garden plant because of its flowering time, sweet fragrance, and ornamental value. However, research into the molecular mechanism that regulates flower development in wintersweet is still limited. In this study, we sought to investigate the [...] Read more.

Wintersweet (Chimonanthus praecox) is a popular garden plant because of its flowering time, sweet fragrance, and ornamental value. However, research into the molecular mechanism that regulates flower development in wintersweet is still limited. In this study, we sought to investigate the molecular characteristics, expression patterns, and potential functions of two C3H-type zinc finger (CZF) protein genes, CpCZF1 and CpCZF2, which were isolated from the wintersweet flowers based on the flower developmental transcriptome database. CpCZF1 and CpCZF2 were more highly expressed in flower organs than in vegetative tissues, and during the flower development, their expression profiles were associated with flower primordial differentiation, especially that of petal and stamen primordial differentiation. Overexpression of either CpCZF1 or CpCZF2 caused alterations on stamens in transgenic Arabidopsis. The expression levels of the stamen identity-related genes, such as AGAMOUS (AG), PISTILLATA (PI), SEPALLATA1 (SEP1), SEPALLATA2 (SEP2), SEPALLATA3 (SEP3), APETALA1 (AP1), APETALA2 (AP2), and boundary gene RABBIT EAR (RBE) were significantly up-regulated in CpCZF1 overexpression lines. Additionally, the transcripts of AG, PI, APETALA3 SEP1-3, AP1, and RBE were markedly increased in CpCZF2 overexpressed plant inflorescences. Moreover, CpCZF1 and CpCZF2 could interact with each other by using yeast two-hybrid and bimolecular fluorescence complementation assays. Our results suggest that CpCZF1 and CpCZF2 may be involved in the regulation of stamen development and cause the formation of abnormal flowers in transgenic Arabidopsis plants. Full article

(This article belongs to the Section Plant Genetics and Genomics)

► Show Figures

Figure 1

2998 KiB

Open AccessArticle

Analysis of Argonaute 4-Associated Long Non-Coding RNA in Arabidopsis thaliana Sheds Novel Insights into Gene Regulation through RNA-Directed DNA Methylation

by Phil Chi Khang Au, Elizabeth S. Dennis and Ming-Bo Wang

Genes 2017, 8(8), 198; https://doi.org/10.3390/genes8080198 - 7 Aug 2017

Cited by 23 | Viewed by 7166

Abstract

RNA-directed DNA methylation (RdDM) is a plant-specific de novo DNA methylation mechanism that requires long noncoding RNA (lncRNA) as scaffold to define target genomic loci. While the role of RdDM in maintaining genome stability is well established, how it regulates protein-coding genes remains [...] Read more.

RNA-directed DNA methylation (RdDM) is a plant-specific de novo DNA methylation mechanism that requires long noncoding RNA (lncRNA) as scaffold to define target genomic loci. While the role of RdDM in maintaining genome stability is well established, how it regulates protein-coding genes remains poorly understood and few RdDM target genes have been identified. In this study, we obtained sequences of RdDM-associated lncRNAs using nuclear RNA immunoprecipitation against ARGONAUTE 4 (AGO4), a key component of RdDM that binds specifically with the lncRNA. Comparison of these lncRNAs with gene expression data of RdDM mutants identified novel RdDM target genes. Surprisingly, a large proportion of these target genes were repressed in RdDM mutants suggesting that they are normally activated by RdDM. These RdDM-activated genes are more enriched for gene body lncRNA than the RdDM-repressed genes. Histone modification and RNA analyses of several RdDM-activated stress response genes detected increased levels of active histone mark and short RNA transcript in the lncRNA-overlapping gene body regions in the ago4 mutant despite the repressed expression of these genes. These results suggest that RdDM, or AGO4, may play a role in maintaining or activating stress response gene expression by directing gene body chromatin modification preventing cryptic transcription. Full article

(This article belongs to the Special Issue RNA Modification)

► Show Figures

Figure 1

516 KiB

Open AccessReview

c-di-AMP: An Essential Molecule in the Signaling Pathways that Regulate the Viability and Virulence of Gram-Positive Bacteria

by Tazin Fahmi, Gary C. Port and Kyu Hong Cho

Genes 2017, 8(8), 197; https://doi.org/10.3390/genes8080197 - 7 Aug 2017

Cited by 76 | Viewed by 8873

Abstract

Signal transduction pathways enable organisms to monitor their external environment and adjust gene regulation to appropriately modify their cellular processes. Second messenger nucleotides including cyclic adenosine monophosphate (c-AMP), cyclic guanosine monophosphate (c-GMP), cyclic di-guanosine monophosphate (c-di-GMP), and cyclic di-adenosine monophosphate (c-di-AMP) play key [...] Read more.

Signal transduction pathways enable organisms to monitor their external environment and adjust gene regulation to appropriately modify their cellular processes. Second messenger nucleotides including cyclic adenosine monophosphate (c-AMP), cyclic guanosine monophosphate (c-GMP), cyclic di-guanosine monophosphate (c-di-GMP), and cyclic di-adenosine monophosphate (c-di-AMP) play key roles in many signal transduction pathways used by prokaryotes and/or eukaryotes. Among the various second messenger nucleotides molecules, c-di-AMP was discovered recently and has since been shown to be involved in cell growth, survival, and regulation of virulence, primarily within Gram-positive bacteria. The cellular level of c-di-AMP is maintained by a family of c-di-AMP synthesizing enzymes, diadenylate cyclases (DACs), and degradation enzymes, phosphodiesterases (PDEs). Genetic manipulation of DACs and PDEs have demonstrated that alteration of c-di-AMP levels impacts both growth and virulence of microorganisms. Unlike other second messenger molecules, c-di-AMP is essential for growth in several bacterial species as many basic cellular functions are regulated by c-di-AMP including cell wall maintenance, potassium ion homeostasis, DNA damage repair, etc. c-di-AMP follows a typical second messenger signaling pathway, beginning with binding to receptor molecules to subsequent regulation of downstream cellular processes. While c-di-AMP binds to specific proteins that regulate pathways in bacterial cells, c-di-AMP also binds to regulatory RNA molecules that control potassium ion channel expression in Bacillus subtilis. c-di-AMP signaling also occurs in eukaryotes, as bacterially produced c-di-AMP stimulates host immune responses during infection through binding of innate immune surveillance proteins. Due to its existence in diverse microorganisms, its involvement in crucial cellular activities, and its stimulating activity in host immune responses, c-di-AMP signaling pathway has become an attractive antimicrobial drug target and therefore has been the focus of intensive study in several important pathogens. Full article

(This article belongs to the Section Microbial Genetics and Genomics)

► Show Figures

Figure 1

2817 KiB

Open AccessReview

Acetylation- and Methylation-Related Epigenetic Proteins in the Context of Their Targets

by Nasir Javaid and Sangdun Choi

Genes 2017, 8(8), 196; https://doi.org/10.3390/genes8080196 - 7 Aug 2017

Cited by 72 | Viewed by 11288

Abstract

The nucleosome surface is covered with multiple modifications that are perpetuated by eight different classes of enzymes. These enzymes modify specific target sites both on DNA and histone proteins, and these modifications have been well identified and termed “epigenetics”. These modifications play critical [...] Read more.

The nucleosome surface is covered with multiple modifications that are perpetuated by eight different classes of enzymes. These enzymes modify specific target sites both on DNA and histone proteins, and these modifications have been well identified and termed “epigenetics”. These modifications play critical roles, either by affecting non-histone protein recruitment to chromatin or by disturbing chromatin contacts. Their presence dictates the condensed packaging of DNA and can coordinate the orderly recruitment of various enzyme complexes for DNA manipulation. This genetic modification machinery involves various writers, readers, and erasers that have unique structures, functions, and modes of action. Regarding human disease, studies have mainly focused on the genetic mechanisms; however, alteration in the balance of epigenetic networks can result in major pathologies including mental retardation, chromosome instability syndromes, and various types of cancers. Owing to its critical influence, great potential lies in developing epigenetic therapies. In this regard, this review has highlighted mechanistic and structural interactions of the main epigenetic families with their targets, which will help to identify more efficient and safe drugs against several diseases. Full article

(This article belongs to the Special Issue Protein-DNA Interactions)

► Show Figures

Figure 1

2293 KiB

Open AccessArticle

Dissecting Tissue-Specific Transcriptomic Responses from Leaf and Roots under Salt Stress in Petunia hybrida Mitchell

by Gonzalo H. Villarino, Qiwen Hu, Michael J. Scanlon, Lukas Mueller, Aureliano Bombarely and Neil S. Mattson

Genes 2017, 8(8), 195; https://doi.org/10.3390/genes8080195 - 3 Aug 2017

Cited by 4 | Viewed by 5319

Abstract

One of the primary objectives of plant biotechnology is to increase resistance to abiotic stresses, such as salinity. Salinity is a major abiotic stress and increasing crop resistant to salt continues to the present day as a major challenge. Salt stress disturbs cellular [...] Read more.

One of the primary objectives of plant biotechnology is to increase resistance to abiotic stresses, such as salinity. Salinity is a major abiotic stress and increasing crop resistant to salt continues to the present day as a major challenge. Salt stress disturbs cellular environment leading to protein misfolding, affecting normal plant growth and causing agricultural losses worldwide. The advent of state-of-the-art technologies such as high throughput mRNA sequencing (RNA-seq) has revolutionized whole-transcriptome analysis by allowing, with high precision, to measure changes in gene expression. In this work, we used tissue-specific RNA-seq to gain insight into the Petunia hybrida transcriptional responses under NaCl stress using a controlled hydroponic system. Roots and leaves samples were taken from a continuum of 48 h of acute 150 mM NaCl. This analysis revealed a set of tissue and time point specific differentially expressed genes, such as genes related to transport, signal transduction, ion homeostasis as well as novel and undescribed genes, such as Peaxi162Scf00003g04130 and Peaxi162Scf00589g00323 expressed only in roots under salt stress. In this work, we identified early and late expressed genes in response to salt stress while providing a core of differentially express genes across all time points and tissues, including the trehalose-6-phosphate synthase 1 (TPS1), a glycosyltransferase reported in salt tolerance in other species. To test the function of the novel petunia TPS1 allele, we cloned and showed that TPS1 is a functional plant gene capable of complementing the trehalose biosynthesis pathway in a yeast tps1 mutant. The list of candidate genes to enhance salt tolerance provided in this work constitutes a major effort to better understand the detrimental effects of salinity in petunia with direct implications for other economically important Solanaceous species. Full article

(This article belongs to the Section Plant Genetics and Genomics)

► Show Figures

Figure 1

5594 KiB

Open AccessArticle

Characterization and Expression Profiling of Camellia sinensis Cinnamate 4-hydroxylase Genes in Phenylpropanoid Pathways

by Jinxin Xia, Yajun Liu, Shengbo Yao, Ming Li, Mengqing Zhu, Keyi Huang, Liping Gao and Tao Xia

Genes 2017, 8(8), 193; https://doi.org/10.3390/genes8080193 - 1 Aug 2017

Cited by 35 | Viewed by 8724

Abstract

Cinnamate 4-hydroxylase (C4H), a cytochrome P450-dependent monooxygenase, participates in the synthesis of numerous polyphenoid compounds, such as flavonoids and lignins. However, the C4H gene number and function in tea plants are not clear. We screened all available transcriptome and genome databases of tea [...] Read more.

Cinnamate 4-hydroxylase (C4H), a cytochrome P450-dependent monooxygenase, participates in the synthesis of numerous polyphenoid compounds, such as flavonoids and lignins. However, the C4H gene number and function in tea plants are not clear. We screened all available transcriptome and genome databases of tea plants and three C4H genes were identified and named CsC4Ha, CsC4Hb, and CsC4Hc, respectively. Both CsC4Ha and CsC4Hb have 1518-bp open reading frames that encode 505-amino acid proteins. CsC4Hc has a 1635-bp open reading frame that encodes a 544-amino acid protein. Enzymatic analysis of recombinant proteins expressed in yeast showed that the three enzymes catalyzed the formation of p-coumaric acid (4-hydroxy trans-cinnamic acid) from trans-cinnamic acid. Quantitative real-time PCR (qRT-PCR) analysis showed that CsC4Ha was highly expressed in the 4th leaf, CsC4Hb was highly expressed in tender leaves, while CsC4Hc was highly expressed in the young stems. The three CsC4Hs were induced with varying degrees by abiotic stress treatments. These results suggest they may have different subcellular localization and different physiological functions. Full article

(This article belongs to the Section Plant Genetics and Genomics)

► Show Figures

Figure 1

3870 KiB

Open AccessReview

Proteins Recognizing DNA: Structural Uniqueness and Versatility of DNA-Binding Domains in Stem Cell Transcription Factors

by Dhanusha Yesudhas, Maria Batool, Muhammad Ayaz Anwar, Suresh Panneerselvam and Sangdun Choi

Genes 2017, 8(8), 192; https://doi.org/10.3390/genes8080192 - 1 Aug 2017

Cited by 27 | Viewed by 17068

Abstract

Proteins in the form of transcription factors (TFs) bind to specific DNA sites that regulate cell growth, differentiation, and cell development. The interactions between proteins and DNA are important toward maintaining and expressing genetic information. Without knowing TFs structures and DNA-binding properties, it [...] Read more.

Proteins in the form of transcription factors (TFs) bind to specific DNA sites that regulate cell growth, differentiation, and cell development. The interactions between proteins and DNA are important toward maintaining and expressing genetic information. Without knowing TFs structures and DNA-binding properties, it is difficult to completely understand the mechanisms by which genetic information is transferred between DNA and proteins. The increasing availability of structural data on protein-DNA complexes and recognition mechanisms provides deeper insights into the nature of protein-DNA interactions and therefore, allows their manipulation. TFs utilize different mechanisms to recognize their cognate DNA (direct and indirect readouts). In this review, we focus on these recognition mechanisms as well as on the analysis of the DNA-binding domains of stem cell TFs, discussing the relative role of various amino acids toward facilitating such interactions. Unveiling such mechanisms will improve our understanding of the molecular pathways through which TFs are involved in repressing and activating gene expression. Full article

(This article belongs to the Special Issue Protein-DNA Interactions)

► Show Figures

Figure 1

5949 KiB

Open AccessArticle

Genome-Wide Analysis Reveals Extensive Changes in LncRNAs during Skeletal Muscle Development in Hu Sheep

by Caifang Ren, Mingtian Deng, Yixuan Fan, Hua Yang, Guomin Zhang, Xu Feng, Fengzhe Li, Dan Wang, Feng Wang and Yanli Zhang

Genes 2017, 8(8), 191; https://doi.org/10.3390/genes8080191 - 1 Aug 2017

Cited by 36 | Viewed by 6098

Abstract

As an important type of noncoding RNA molecules, long non-coding RNAs (lncRNAs) act as versatile players in various biological processes. However, little is known about lncRNA regulators during sheep muscle growth. To explore functional lncRNAs during sheep muscle growth, we systematically investigated lncRNAs [...] Read more.

As an important type of noncoding RNA molecules, long non-coding RNAs (lncRNAs) act as versatile players in various biological processes. However, little is known about lncRNA regulators during sheep muscle growth. To explore functional lncRNAs during sheep muscle growth, we systematically investigated lncRNAs using strand-specific Ribo-Zero RNA sequencing at three key developmental stages in Hu sheep. A total of 6924 lncRNAs were obtained, and the differentially expressed lncRNAs and genes were screened from (control vs. experiment) fetus vs. lamb, lamb vs. adult, and fetus vs. adult comparisons, respectively. The quantitative real-time polymerase chain reaction (qRT-PCR) analysis results correlated well with the sequencing data. Moreover, functional annotation analysis based on the Gene Ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) databases showed that the target genes of the differentially expressed lncRNAs were significantly enriched in organ morphogenesis, skeletal system development as well as response to stimulus and some other terms related to muscle. Furthermore, a co-expression network of the differentially expressed target genes and lncRNAs was constructed and well-known muscle growth regulators such as retrotransposon-like 1 and Junctophilin-2 were included. Finally, we investigated the expression profiles of seven lncRNAs and their target genes, and found that they played vital roles in muscle growth. This study extends the sheep muscle lncRNA database and provides novel candidate regulators for future genetic and molecular studies on sheep muscle growth, which is helpful for optimizing the production of mutton. Full article

► Show Figures

Figure 1

Journal Menu

Journal Browser

Genes, Volume 8, Issue 8 (August 2017) – 18 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI