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Chromatin Dynamics
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Chromatin Dynamics

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Human Genomics and Genetic Diseases".

Deadline for manuscript submissions: closed (30 April 2015) | Viewed by 194367

Special Issue Editor

Prof. Dr. Jessica Tyler

E-Mail Website
Guest Editor
Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10021, USA
Interests: chromatin assembly; histone modifications; chromatin remodeling; DNA double strand break repair; replicative aging
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Our understanding of chromatin has increased exponentially since German anatomist Walther Flemming first coined the word in 1879 to describe the readily stainable substance in a cell nucleus. We now know that chromatin is highly dynamic, mediated via histone post-translational modifications, DNA methylation, histone variants, ATP-dependent nucleosome remodeling, higher order chromatin compaction, and inter- and intra-chromosome interactions. The central function of chromatin dynamics is to reveal, or block, access to specific DNA sequences in a manner that is dependent on the particular stage of the cell cycle, development, differentiation, and environment of the cell. In doing so, chromatin dynamics enables the cell to tightly regulate all the fundamental activities of the genome, including DNA replication, transcription, repair, recombination, and mitosis. Not surprisingly, many human diseases are caused when the machinery that mediates chromatin dynamics goes awry. In a single issue of Genes in Spring of 2015, we would like to summarize the current state of our understanding of chromatin dynamics by showcasing the best research from around the world. We welcome reviews and original articles in the area of chromatin dynamics, including causal studies relating disruption of the machinery that modulates chromatin remodeling to human disease.

Prof. Dr. Jessica Tyler
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Genes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.


Keywords

  • chromatin remodeling
  • histone variants
  • histone modifications
  • histone chaperones
  • chromosome territories

Published Papers (19 papers)

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Research

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8131 KiB  
Article
Epigenetic Heterogeneity of B-Cell Lymphoma: Chromatin Modifiers
by Lydia Hopp, Lilit Nersisyan, Henry Löffler-Wirth, Arsen Arakelyan and Hans Binder
Genes 2015, 6(4), 1076-1112; https://doi.org/10.3390/genes6041076 - 21 Oct 2015
Cited by 14 | Viewed by 9545
Abstract
We systematically studied the expression of more than fifty histone and DNA (de)methylating enzymes in lymphoma and healthy controls. As a main result, we found that the expression levels of nearly all enzymes become markedly disturbed in lymphoma, suggesting deregulation of large parts [...] Read more.
We systematically studied the expression of more than fifty histone and DNA (de)methylating enzymes in lymphoma and healthy controls. As a main result, we found that the expression levels of nearly all enzymes become markedly disturbed in lymphoma, suggesting deregulation of large parts of the epigenetic machinery. We discuss the effect of DNA promoter methylation and of transcriptional activity in the context of mutated epigenetic modifiers such as EZH2 and MLL2. As another mechanism, we studied the coupling between the energy metabolism and epigenetics via metabolites that act as cofactors of JmjC-type demethylases. Our study results suggest that Burkitt’s lymphoma and diffuse large B-cell Lymphoma differ by an imbalance of repressive and poised promoters, which is governed predominantly by the activity of methyltransferases and the underrepresentation of demethylases in this regulation. The data further suggest that coupling of epigenetics with the energy metabolism can also be an important factor in lymphomagenesis in the absence of direct mutations of genes in metabolic pathways. Understanding of epigenetic deregulation in lymphoma and possibly in cancers in general must go beyond simple schemes using only a few modes of regulation. Full article
(This article belongs to the Special Issue Chromatin Dynamics)
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Article
Epigenetic Heterogeneity of B-Cell Lymphoma: DNA Methylation, Gene Expression and Chromatin States
by Lydia Hopp, Henry Löffler-Wirth and Hans Binder
Genes 2015, 6(3), 812-840; https://doi.org/10.3390/genes6030812 - 07 Sep 2015
Cited by 26 | Viewed by 13088
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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Review

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339 KiB  
Review
Super Enhancers in Cancers, Complex Disease, and Developmental Disorders
by Adrienne R. Niederriter, Arushi Varshney, Stephen C. J. Parker and Donna M. Martin
Genes 2015, 6(4), 1183-1200; https://doi.org/10.3390/genes6041183 - 09 Nov 2015
Cited by 60 | Viewed by 12276
Abstract
Recently, unique areas of transcriptional regulation termed super-enhancers have been identified and implicated in human disease. Defined by their magnitude of size, transcription factor density, and binding of transcriptional machinery, super-enhancers have been associated with genes driving cell differentiation. While their functions are [...] Read more.
Recently, unique areas of transcriptional regulation termed super-enhancers have been identified and implicated in human disease. Defined by their magnitude of size, transcription factor density, and binding of transcriptional machinery, super-enhancers have been associated with genes driving cell differentiation. While their functions are not completely understood, it is clear that these regions driving high-level transcription are susceptible to perturbation, and trait-associated single nucleotide polymorphisms (SNPs) occur within super-enhancers of disease-relevant cell types. Here we review evidence for super-enhancer involvement in cancers, complex diseases, and developmental disorders and discuss interactions between super-enhancers and cofactors/chromatin regulators. Full article
(This article belongs to the Special Issue Chromatin Dynamics)
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701 KiB  
Review
Impact of Chromatin on HIV Replication
by Luis M. Agosto, Matthew Gagne and Andrew J. Henderson
Genes 2015, 6(4), 957-976; https://doi.org/10.3390/genes6040957 - 30 Sep 2015
Cited by 18 | Viewed by 7693
Abstract
Chromatin influences Human Immunodeficiency Virus (HIV) integration and replication. This review highlights critical host factors that influence chromatin structure and organization and that also impact HIV integration, transcriptional regulation and latency. Furthermore, recent attempts to target chromatin associated factors to reduce the HIV [...] Read more.
Chromatin influences Human Immunodeficiency Virus (HIV) integration and replication. This review highlights critical host factors that influence chromatin structure and organization and that also impact HIV integration, transcriptional regulation and latency. Furthermore, recent attempts to target chromatin associated factors to reduce the HIV proviral load are discussed. Full article
(This article belongs to the Special Issue Chromatin Dynamics)
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768 KiB  
Review
Epigenetic Therapy for Solid Tumors: Highlighting the Impact of Tumor Hypoxia
by Shaliny Ramachandran, Jonathan Ient, Eva-Leonne Göttgens, Adam J. Krieg and Ester M. Hammond
Genes 2015, 6(4), 935-956; https://doi.org/10.3390/genes6040935 - 25 Sep 2015
Cited by 44 | Viewed by 11108
Abstract
In the last few decades, epigenetics has emerged as an exciting new field in development and disease, with a more recent focus towards cancer. Epigenetics has classically referred to heritable patterns of gene expression, primarily mediated through DNA methylation patterns. More recently, it [...] Read more.
In the last few decades, epigenetics has emerged as an exciting new field in development and disease, with a more recent focus towards cancer. Epigenetics has classically referred to heritable patterns of gene expression, primarily mediated through DNA methylation patterns. More recently, it has come to include the reversible chemical modification of histones and DNA that dictate gene expression patterns. Both the epigenetic up-regulation of oncogenes and downregulation of tumor suppressors have been shown to drive tumor development. Current clinical trials for cancer therapy include pharmacological inhibition of DNA methylation and histone deacetylation, with the aim of reversing these cancer-promoting epigenetic changes. However, the DNA methyltransferase and histone deacetylase inhibitors have met with less than promising results in the treatment of solid tumors. Regions of hypoxia are a common occurrence in solid tumors. Tumor hypoxia is associated with increased aggressiveness and therapy resistance, and importantly, hypoxic tumor cells have a distinct epigenetic profile. In this review, we provide a summary of the recent clinical trials using epigenetic drugs in solid tumors, discuss the hypoxia-induced epigenetic changes and highlight the importance of testing the epigenetic drugs for efficacy against the most aggressive hypoxic fraction of the tumor in future preclinical testing. Full article
(This article belongs to the Special Issue Chromatin Dynamics)
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652 KiB  
Review
Replication Stress: A Lifetime of Epigenetic Change
by Simran Khurana and Philipp Oberdoerffer
Genes 2015, 6(3), 858-877; https://doi.org/10.3390/genes6030858 - 11 Sep 2015
Cited by 26 | Viewed by 11471
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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1246 KiB  
Review
Chromatin Insulators and Topological Domains: Adding New Dimensions to 3D Genome Architecture
by Navneet K. Matharu and Sajad H. Ahanger
Genes 2015, 6(3), 790-811; https://doi.org/10.3390/genes6030790 - 01 Sep 2015
Cited by 13 | Viewed by 13601
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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2251 KiB  
Review
Chromatin Dynamics in Vivo: A Game of Musical Chairs
by Daniël P. Melters, Jonathan Nye, Haiqing Zhao and Yamini Dalal
Genes 2015, 6(3), 751-776; https://doi.org/10.3390/genes6030751 - 07 Aug 2015
Cited by 25 | Viewed by 9073
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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2966 KiB  
Review
Contribution of Topological Domains and Loop Formation to 3D Chromatin Organization
by Vuthy Ea, Marie-Odile Baudement, Annick Lesne and Thierry Forné
Genes 2015, 6(3), 734-750; https://doi.org/10.3390/genes6030734 - 27 Jul 2015
Cited by 44 | Viewed by 18034
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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3837 KiB  
Review
The Structural Determinants behind the Epigenetic Role of Histone Variants
by Manjinder S. Cheema and Juan Ausió
Genes 2015, 6(3), 685-713; https://doi.org/10.3390/genes6030685 - 23 Jul 2015
Cited by 24 | Viewed by 9033
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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335 KiB  
Review
Chromatin Dynamics in Lineage Commitment and Cellular Reprogramming
by Virlana M. Shchuka, Nakisa Malek-Gilani, Gurdeep Singh, Lida Langroudi, Navroop K. Dhaliwal, Sakthi D. Moorthy, Scott Davidson, Neil N. Macpherson and Jennifer A. Mitchell
Genes 2015, 6(3), 641-661; https://doi.org/10.3390/genes6030641 - 17 Jul 2015
Cited by 12 | Viewed by 11320
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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382 KiB  
Review
Nucleosome Dancing at the Tempo of Histone Tail Acetylation
by Angélique Galvani and Christophe Thiriet
Genes 2015, 6(3), 607-621; https://doi.org/10.3390/genes6030607 - 15 Jul 2015
Cited by 30 | Viewed by 7041
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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422 KiB  
Review
RNF20-SNF2H Pathway of Chromatin Relaxation in DNA Double-Strand Break Repair
by Akihiro Kato and Kenshi Komatsu
Genes 2015, 6(3), 592-606; https://doi.org/10.3390/genes6030592 - 14 Jul 2015
Cited by 14 | Viewed by 9539
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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147 KiB  
Review
Chromatin Dynamics in the Regulation of CFTR Expression
by Nehal Gosalia and Ann Harris
Genes 2015, 6(3), 543-558; https://doi.org/10.3390/genes6030543 - 13 Jul 2015
Cited by 22 | Viewed by 6667
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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374 KiB  
Review
One, Two, Three: Polycomb Proteins Hit All Dimensions of Gene Regulation
by Stefania Del Prete, Pawel Mikulski, Daniel Schubert and Valérie Gaudin
Genes 2015, 6(3), 520-542; https://doi.org/10.3390/genes6030520 - 10 Jul 2015
Cited by 16 | Viewed by 8437
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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516 KiB  
Review
From Structural Variation of Gene Molecules to Chromatin Dynamics and Transcriptional Bursting
by Hinrich Boeger, Robert Shelansky, Heta Patel and Christopher R. Brown
Genes 2015, 6(3), 469-483; https://doi.org/10.3390/genes6030469 - 30 Jun 2015
Cited by 9 | Viewed by 6136
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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128 KiB  
Review
The Fork in the Road: Histone Partitioning During DNA Replication
by Anthony T. Annunziato
Genes 2015, 6(2), 353-371; https://doi.org/10.3390/genes6020353 - 23 Jun 2015
Cited by 43 | Viewed by 6905
Abstract
In the following discussion the distribution of histones at the replication fork is examined, with specific attention paid to the question of H3/H4 tetramer "splitting." After a presentation of early experiments surrounding this topic, more recent contributions are detailed. The implications of these [...] Read more.
In the following discussion the distribution of histones at the replication fork is examined, with specific attention paid to the question of H3/H4 tetramer "splitting." After a presentation of early experiments surrounding this topic, more recent contributions are detailed. The implications of these findings with respect to the transmission of histone modifications and epigenetic models are also addressed. Full article
(This article belongs to the Special Issue Chromatin Dynamics)
1077 KiB  
Review
PHF6 Degrees of Separation: The Multifaceted Roles of a Chromatin Adaptor Protein
by Matthew A.M. Todd, Danton Ivanochko and David J. Picketts
Genes 2015, 6(2), 325-352; https://doi.org/10.3390/genes6020325 - 19 Jun 2015
Cited by 34 | Viewed by 8809
Abstract
The importance of chromatin regulation to human disease is highlighted by the growing number of mutations identified in genes encoding chromatin remodeling proteins. While such mutations were first identified in severe developmental disorders, or in specific cancers, several genes have been implicated in [...] Read more.
The importance of chromatin regulation to human disease is highlighted by the growing number of mutations identified in genes encoding chromatin remodeling proteins. While such mutations were first identified in severe developmental disorders, or in specific cancers, several genes have been implicated in both, including the plant homeodomain finger protein 6 (PHF6) gene. Indeed, germline mutations in PHF6 are the cause of the Börjeson–Forssman–Lehmann X-linked intellectual disability syndrome (BFLS), while somatic PHF6 mutations have been identified in T-cell acute lymphoblastic leukemia (T-ALL) and acute myeloid leukemia (AML). Studies from different groups over the last few years have made a significant impact towards a functional understanding of PHF6 protein function. In this review, we summarize the current knowledge of PHF6 with particular emphasis on how it interfaces with a distinct set of interacting partners and its functional roles in the nucleoplasm and nucleolus. Overall, PHF6 is emerging as a key chromatin adaptor protein critical to the regulation of neurogenesis and hematopoiesis. Full article
(This article belongs to the Special Issue Chromatin Dynamics)
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1433 KiB  
Review
Chromatin Remodelers: From Function to Dysfunction
by Gernot Längst and Laura Manelyte
Genes 2015, 6(2), 299-324; https://doi.org/10.3390/genes6020299 - 12 Jun 2015
Cited by 112 | Viewed by 13087
Abstract
Chromatin remodelers are key players in the regulation of chromatin accessibility and nucleosome positioning on the eukaryotic DNA, thereby essential for all DNA dependent biological processes. Thus, it is not surprising that upon of deregulation of those molecular machines healthy cells can turn [...] Read more.
Chromatin remodelers are key players in the regulation of chromatin accessibility and nucleosome positioning on the eukaryotic DNA, thereby essential for all DNA dependent biological processes. Thus, it is not surprising that upon of deregulation of those molecular machines healthy cells can turn into cancerous cells. Even though the remodeling enzymes are very abundant and a multitude of different enzymes and chromatin remodeling complexes exist in the cell, the particular remodeling complex with its specific nucleosome positioning features must be at the right place at the right time in order to ensure the proper regulation of the DNA dependent processes. To achieve this, chromatin remodeling complexes harbor protein domains that specifically read chromatin targeting signals, such as histone modifications, DNA sequence/structure, non-coding RNAs, histone variants or DNA bound interacting proteins. Recent studies reveal the interaction between non-coding RNAs and chromatin remodeling complexes showing importance of RNA in remodeling enzyme targeting, scaffolding and regulation. In this review, we summarize current understanding of chromatin remodeling enzyme targeting to chromatin and their role in cancer development. Full article
(This article belongs to the Special Issue Chromatin Dynamics)
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