The packaging of DNA into strings of nucleosomes is one of the features that allows eukaryotic cells to tightly regulate gene expression. The ordered disassembly of nucleosomes permits RNA polymerase ...II (Pol II) to access the DNA, whereas nucleosomal reassembly impedes access, thus preventing transcription and mRNA synthesis. Chromatin modifications, chromatin remodellers, histone chaperones and histone variants regulate nucleosomal dynamics during transcription. Disregulation of nucleosome dynamics results in aberrant transcription initiation, producing non-coding RNAs. Ongoing research is elucidating the molecular mechanisms that regulate chromatin structure during transcription by preventing histone exchange, thereby limiting non-coding RNA expression.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Alterations of chromatin structure have been shown to be crucial for response to cell signaling and for programmed gene expression in development. Posttranslational histone modifications influence ...changes in chromatin structure both directly and by targeting or activating chromatin-remodeling complexes. Histone modifications intersect with cell signaling pathways to control gene expression and can act combinatorially to enforce or reverse epigenetic marks in chromatin. Through their recognition by protein complexes with enzymatic activities cross talk is established between different modifications and with other epigenetic pathways, including noncoding RNAs (ncRNAs) and DNA methylation. Here, we review the functions of histone modifications and their exploitation in the programming of gene expression during several events in development.
Modifications of histones play important roles in balancing transcriptional output. The discovery of acyl marks, besides histone acetylation, has added to the functional diversity of histone ...modifications. Since all modifications use metabolic intermediates as substrates for chromatin-modifying enzymes, the prevalent landscape of histone modifications in any cell type is a snapshot of its metabolic status. Here, we review some of the current findings of how differential use of histone acylations regulates gene expression as response to metabolic changes and differentiation programs.
The identification of non-acetyl histone acylations has expanded the repertoire of modifications on histone tails. Different histone acylations are sensitive to the metabolic status of cells and may connect metabolism to gene regulation.
Eukaryotic genomes are packaged into chromatin, a highly organized structure consisting of DNA and histone proteins. All nuclear processes take place in the context of chromatin. Modifications of ...either DNA or histone proteins have fundamental effects on chromatin structure and function, and thus influence processes such as transcription, replication or recombination. In this review we highlight histone modifications specifically associated with gene transcription by RNA polymerase II and summarize their genomic distributions. Finally, we discuss how (mis-)regulation of these histone modifications perturbs chromatin organization over coding regions and results in the appearance of aberrant, intragenic transcription. This article is part of a Special Issue entitled: RNA polymerase II Transcript Elongation.
► Histone modifications influence chromatin organization during transcription elongation. ► Histone chaperones and H2B ubiquitination maintain nucleosome levels over gene bodies. ► Disruption of histone H3K36 methylation leads to increased histone exchange and altered, hyperacetylated chromatin. ► Perturbation of chromatin structure over gene bodies exposes cryptic promoters. ► Cryptic transcripts are polyadenylated and even translated — their function is unclear though.
Over the past 10 years, the study of histone acetyltransferases (HATs) has advanced significantly, and a number of HATs have been isolated from various organisms. It emerged that HATs are highly ...diverse and generally contain multiple subunits. The functions of the catalytic subunit depend largely on the context of the other subunits in the complex. We are just beginning to understand the specialized roles of HAT complexes in chromosome decondensation, DNA-damage repair and the modification of non-histone substrates, as well as their role in the broader epigenetic landscape, including the role of protein domains within HAT complexes and the dynamic interplay between HAT complexes and existing histone modifications.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
6.
Readers of histone modifications Yun, Miyong; Wu, Jun; Workman, Jerry L ...
Cell research,
04/2011, Letnik:
21, Številka:
4
Journal Article
Recenzirano
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Histone modifications not only play important roles in regulating chromatin structure and nuclear processes but also can be passed to daughter cells as epigenetic marks. Accumulating evidence ...suggests that the key function of histone modifications is to signal for recruitment or activity of downstream effectors. Here, we discuss the latest discovery of histone-modification readers and how the modification language is interpreted.
Chromatin structure imposes significant obstacles on all aspects of transcription that are mediated by RNA polymerase II. The dynamics of chromatin structure are tightly regulated through multiple ...mechanisms including histone modification, chromatin remodeling, histone variant incorporation, and histone eviction. In this Review, we highlight advances in our understanding of chromatin regulation and discuss how such regulation affects the binding of transcription factors as well as the initiation and elongation steps of transcription.
There are many large protein complexes involved in transcription in a chromatin context. However, recent studies on the SAGA coactivator complex are generating new paradigms for how the components of ...these complexes function, both independently and in concert. This review highlights the initial discovery of the canonical SAGA complex 23 years ago, our evolving understanding of its modular structure and the relevance of its modular nature for its coactivator function in gene regulation.
Recent reports reinforce the notion that nucleosomes are highly dynamic in response to the process of transcription. Nucleosomes are displaced at promoters during gene activation in a process that ...involves histone modification, ATP-dependent nucleosome remodeling complexes, histone chaperones and perhaps histone variants. During transcription elongation nucleosomes are acetylated and transferred behind RNA polymerase II where they are required to suppress spurious transcription initiation within the body of the gene. It is becoming increasingly clear that the eukaryotic transcriptional machinery is adapted to exploit the presence of nucleosomes in very sophisticated ways.
Nucleosome remodeling and epigenetics Becker, Peter B; Workman, Jerry L
Cold Spring Harbor perspectives in biology,
2013-Sep-01, 2013-09-01, 20130901, Letnik:
5, Številka:
9
Journal Article
Recenzirano
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Eukaryotic chromatin is kept flexible and dynamic to respond to environmental, metabolic, and developmental cues through the action of a family of so-called "nucleosome remodeling" ATPases. ...Consistent with their helicase ancestry, these enzymes experience conformation changes as they bind and hydrolyze ATP. At the same time they interact with DNA and histones, which alters histone-DNA interactions in target nucleosomes. Their action may lead to complete or partial disassembly of nucleosomes, the exchange of histones for variants, the assembly of nucleosomes, or the movement of histone octamers on DNA. "Remodeling" may render DNA sequences accessible to interacting proteins or, conversely, promote packing into tightly folded structures. Remodeling processes participate in every aspect of genome function. Remodeling activities are commonly integrated with other mechanisms such as histone modifications or RNA metabolism to assemble stable, epigenetic states.
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