Histone exchange, chromatin structure and the regulation of transcription

Venkatesh, Swaminathan; Workman, Jerry L.

doi:10.1038/nrm3941

Cited by 820 publications

(725 citation statements)

References 163 publications

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“…However, for a eukaryotic system, the nucleosome, which contains eight subunits of histone proteins, provides another layer of structural complexity, which prevents Pol II from accessing promoters, transcription initiation, and elongation. There is abundant evidence showing that ATP-dependent chromatin remodelers, such as switch/sucrose nonfermentable (SWI/SNF), act to alter nucleosome or chromatin architecture via histone subunit exchange, ejection, and spatial reorganization (i.e., by sliding) (53)(54)(55). Based on our findings, we propose a possible mechanism in which the cleavage of the highly charged histone tails lead to weaker association between DNA and histone subunits so as to the final depletion of histone subunits from nucleosome and creation of nucleosome-free regions (Fig.…”

Section: Discussionmentioning

confidence: 99%

Clipping of arginine-methylated histone tails by JMJD5 and JMJD7

Liu

Wang

Lee

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Two of the unsolved, important questions about epigenetics are: do histone arginine demethylases exist, and is the removal of histone tails by proteolysis a major epigenetic modification process? Here, we report that two orphan Jumonji C domain (JmjC)-containing proteins, JMJD5 and JMJD7, have divalent cationdependent protease activities that preferentially cleave the tails of histones 2, 3, or 4 containing methylated arginines. After the initial specific cleavage, JMJD5 and JMJD7, acting as aminopeptidases, progressively digest the C-terminal products. JMJD5-deficient fibroblasts exhibit dramatically increased levels of methylated arginines and histones. Furthermore, depletion of JMJD7 in breast cancer cells greatly decreases cell proliferation. The protease activities of JMJD5 and JMJD7 represent a mechanism for removal of histone tails bearing methylated arginine residues and define a potential mechanism of transcription regulation.histone tail | arginine methylation | clipping | JMJD5/7

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Section: Discussionmentioning

confidence: 99%

Clipping of arginine-methylated histone tails by JMJD5 and JMJD7

Liu

Wang

Lee

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…Importantly, the existence of PANS is a consequence of the modular nature of the nucleosome, facilitating the histone exchange process, which involves the removal of parts of the nucleosome or the entire nucleosome, followed by replacement with newly synthesized histones including variant histones. The histone exchange, which is also known as histone turnover, has many implications for the composition, structure, and function of different genomic regions and it is necessary to tightly regulate gene expression (18).…”

Section: Introductionmentioning

confidence: 99%

Partially Assembled Nucleosome Structures at Atomic Detail

Rychkov

Ilatovskiy

Nazarov

et al. 2017

Biophysical Journal

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The evidence is now overwhelming that partially assembled nucleosome states (PANS) are as important as the canonical nucleosome structure for the understanding of how accessibility to genomic DNA is regulated in cells. We use a combination of molecular dynamics simulation and atomic force microscopy to deliver, in atomic detail, structural models of three key PANS: the hexasome (H2A$H2B)$(H3$H4) 2 , the tetrasome (H3$H4) 2 , and the disome (H3$H4). Despite fluctuations of the conformation of the free DNA in these structures, regions of protected DNA in close contact with the histone core remain stable, thus establishing the basis for the understanding of the role of PANS in DNA accessibility regulation. On average, the length of protected DNA in each structure is roughly 18 basepairs per histone protein. Atomistically detailed PANS are used to explain experimental observations; specifically, we discuss interpretation of atomic force microscopy, Fö rster resonance energy transfer, and small-angle x-ray scattering data obtained under conditions when PANS are expected to exist. Further, we suggest an alternative interpretation of a recent genome-wide study of DNA protection in active chromatin of fruit fly, leading to a conclusion that the three PANS are present in actively transcribing regions in a substantial amount. The presence of PANS may not only be a consequence, but also a prerequisite for fast transcription in vivo.

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“…The basic repeating unit of chromatin is the nucleosome, which consists of a histone octamer enwrapped by 147 bp of DNA, which is organized into two superhelical turns (Luger et al , 1997). Spatial and temporal regulation of specific chromatin loci by dynamic assembly of nucleosomes is essential for the control of DNA‐templated processes such as replication, DNA damage repair, and gene regulation (Venkatesh & Workman, 2015). The nucleosome serves as a general transcriptional repressor, and promoter nucleosome removal is an early step in gene activation (Becker & Horz, 2002; Bryant et al , 2008).…”

Section: Introductionmentioning

confidence: 99%

Structural evidence for Nap1‐dependent H2A–H2B deposition and nucleosome assembly

et al. 2016

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Nap1 is a histone chaperone involved in the nuclear import of H2A–H2B and nucleosome assembly. Here, we report the crystal structure of Nap1 bound to H2A–H2B together with in vitro and in vivo functional studies that elucidate the principles underlying Nap1‐mediated H2A–H2B chaperoning and nucleosome assembly. A Nap1 dimer provides an acidic binding surface and asymmetrically engages a single H2A–H2B heterodimer. Oligomerization of the Nap1–H2A–H2B complex results in burial of surfaces required for deposition of H2A–H2B into nucleosomes. Chromatin immunoprecipitation‐exonuclease (ChIP‐exo) analysis shows that Nap1 is required for H2A–H2B deposition across the genome. Mutants that interfere with Nap1 oligomerization exhibit severe nucleosome assembly defects showing that oligomerization is essential for the chaperone function. These findings establish the molecular basis for Nap1‐mediated H2A–H2B deposition and nucleosome assembly.

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Histone exchange, chromatin structure and the regulation of transcription

Cited by 820 publications

References 163 publications

Clipping of arginine-methylated histone tails by JMJD5 and JMJD7

Clipping of arginine-methylated histone tails by JMJD5 and JMJD7

Partially Assembled Nucleosome Structures at Atomic Detail

Structural evidence for Nap1‐dependent H2A–H2B deposition and nucleosome assembly

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