Accessibility of the histone H3 tail in the nucleosome for binding of paired readers

Gatchalian, Jovylyn; Wang, Xiaodong; Ikebe, Jinzen; Cox, Khan L.; Tencer, Adam H.; Zhang, Yi; Burge, Nathaniel L.; Luo, Dejun; Gibson, Matthew D.; Musselman, Catherine A.; Poirier, Michael G.; Kono, Hidetoshi; Hayes, Jeffrey J.; Kutateladze, Tatiana G.

doi:10.1038/s41467-017-01598-x

Cited by 70 publications

(85 citation statements)

References 53 publications

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“…In this study, we find that, in the absence of salt, accessibility of the nucleosomal H3 tail is increased by a factor of ~16 upon H2A/H2B dimer loss. These results align with investigations into the linked PHD fingers of CHD4, which bind the H3 tails in an 80bp-tetrasome with greater affinity than the 147bp-nucleosome 41 . This suggests that nucleosome composition will modulate accessibility of chromatin-associated proteins to the H3 tail.…”

Section: Discussionsupporting

confidence: 82%

“…Previous studies addressing histone tail accessibility in the context of the nucleosome have shown that the tails are significantly occluded within the nucleosome as compared to histone peptides or refolded histones 32,39,41,42 . In the case of the H3 tail, accessibility to chemical modification is reduced by a factor of ~250 at 50mM NaCl and ~10 at 150mM NaCl 41 . It has been proposed that accessibility to the H3 tail could be modulated by a number of factors including histone PTMs and DNA dynamics.…”

Section: Discussionmentioning

confidence: 99%

“…Proteolysis kinetics-We treated the experimental data for site exposure on the H3 tails probed via trypsin proteolysis in the same manner as site exposure on DNA probed via restriction enzymes 38,40 and in a similar manner as site exposure on histone tails probed via chemical modification 39,41 . These other experiments were designed for digestion and modification at single sites within the nucleosome.…”

Section: Analysis Of Trypsin Proteolysis Assaysmentioning

confidence: 99%

“…In this limit, there is a first-order dependence of the observed rate constant (kobs) on enzyme concentration. Site exposure on nucleosomal DNA and H2B tails were shown to be in limit of rapid pre-equilibrium within the experimental contexts of 40 and 39 , and the assumption of rapid pre-equilibrium was made for the H3 tail in 41 . Thus, it is likely that site exposure on nucleosomal and subnucleosomal H3 tails is also in the limit of rapid pre-equilibrium in the proteolysis experiments described here.…”

Section: Analysis Of Trypsin Proteolysis Assaysmentioning

confidence: 99%

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Nucleosome composition regulates the histone H3 tail conformational ensemble and accessibility

Morrison

Baweja

Poirier

et al. 2020

Preprint

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AbstractSub-nucleosomal complexes including hexasomes and tetrasomes have been identified as intermediates in nucleosome assembly and disassembly. Their formation is promoted by certain histone chaperones and ATP-dependent remodelers, as well as through transcription by RNA polymerase II. In addition, hexasomes appear to be maintained in transcribed genes and could be an important regulatory factor. While nucleosome composition affects the structure and accessibility of the nucleosomal DNA, its influence on the histone tails is largely unknown. Previously, we found that the H3 tail accessibly is occluded in the context of the nucleosome due to interactions with DNA (Morrison et al, 2018). Here, we investigate the conformational dynamics of the H3 tail in the hexasome and tetrasome. Using a combination of NMR spectroscopy, MD simulations, and trypsin proteolysis, we find that the conformational ensemble of the H3 tail is regulated by nucleosome composition. Similar to what we previously found for the nucleosome, the H3 tails bind robustly to DNA within the hexasome and tetrasome, but upon loss of the H2A/H2B dimer, we determined that the adjacent H3 tail has an altered conformational ensemble, increase in dynamics, and increase in accessibility. Similar to observations of DNA dynamics, this is seen to be asymmetric in the hexasome. Our results indicate that nucleosome composition has the potential to regulate chromatin signaling at the histone tails and ultimately help shape the chromatin landscape.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Analysis Of Trypsin Proteolysis Assaysmentioning

confidence: 99%

Section: Analysis Of Trypsin Proteolysis Assaysmentioning

confidence: 99%

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Nucleosome composition regulates the histone H3 tail conformational ensemble and accessibility

Morrison

Baweja

Poirier

et al. 2020

Preprint

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“…The slow passage of RNAPII through the 5' regions of genes increases the opportunity for HATs to access the histone tails resulting in increased acetylation in these regions. In support of this mechanism, the H3 tail becomes ten-fold less accessible when assembled into nucleosomes in vitro 53 and HAT activity is enhanced by disrupting interactions between DNA and the H3 tail 54 . Moreover, we show that nucleosome favoring sequences tend to accumulate both RNAPII and histone acetylation.…”

Section: Discussionmentioning

confidence: 94%

The majority of histone acetylation is a consequence of transcription

Martin

Brind’Amour

Jensen

et al. 2019

Preprint

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Histone acetylation is a ubiquitous hallmark of transcriptional activity, but whether the link is of a causal or consequential nature is still a matter of debate. In this study we resolve this question. Using both immunoblot analysis and chromatin immunoprecipitation-sequencing (ChIP-seq) in S. cerevisiae, we show that the majority of histone acetylation is dependent on transcription. Loss of histone H4 acetylation upon transcription inhibition is partially explained by depletion of histone acetyltransferases (HATs) from gene bodies, implicating transcription in HAT targeting. Despite this, HAT occupancy alone poorly predicts histone acetylation, suggesting that HAT activity is regulated at a step postrecruitment. Collectively, these data show that the majority of histone acetylation is a consequence of RNAPII promoting both the recruitment and activity of histone acetyltransferases.

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Rise of the Chromodomain Helicase DNA‐Binding (CHD) Chromatin Remodelling Machines

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2023

Encyclopedia of Life Sciences

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Vital processes such as transcription, repair, replication and recombination continuously shape cellular chromatin landscape. The chromodomain helicase DNA‐binding (CHD) family of enzymes regulate chromatin dynamics by utilising energy from ATP hydrolysis to alter nucleosomal position, structure and composition, thereby modulating accessibility of the underlying DNA sequence. The CHD enzymes are highly conserved in evolution, and genetic studies in fungi, plants and animals demonstrate their critical roles in regulation of cellular identity and fate and organismal development. Advances in genomic studies over the past two decades led to the identification of frequent DNA copy‐number alterations, mutations and aberrant expression of CHDs in human malignancies and various disorders, highlighting their importance as relevant biomarkers or targets for therapeutic intervention. Key Concepts CHD family of enzymes (CHD1‐9) are evolutionary conserved ATP‐dependent chromatin remodelers that mobilise nucleosomes to regulate DNA‐templated processes, such as transcription, replication and repair. They are critical for normal organismal development and are frequently mutated in human disorders and cancers. Chromodomain helicase DNA‐binding proteins (CHD1‐9) are evolutionary conserved family of ATP‐dependent chromatin remodelers that mobilise nucleosomes to regulate DNA‐templated processes such as transcription, replication and DNA repair. CHD enzymes share a common domain structure: two N‐terminal chromodomains, a central ATPase/helicase domain, and a C‐terminal DNA‐binding domain. CHD proteins play crucial roles in diverse cellular processes, including embryonic development, stem cell maintenance and differentiation, and tissue‐specific gene expression. Dysregulation of CHD proteins has been associated with various human diseases, including cancer and neurodevelopmental disorders. CHD proteins are attractive targets for the development of new therapies for diseases associated with chromatin dysfunction. Understanding the molecular mechanisms underlying the function of CHD proteins may pave the way for the development of new drugs that target these proteins and improve the treatment of a variety of human diseases.

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Accessibility of the histone H3 tail in the nucleosome for binding of paired readers

Cited by 70 publications

References 53 publications

Nucleosome composition regulates the histone H3 tail conformational ensemble and accessibility

Nucleosome composition regulates the histone H3 tail conformational ensemble and accessibility

The majority of histone acetylation is a consequence of transcription

Rise of the Chromodomain Helicase DNA‐Binding (CHD) Chromatin Remodelling Machines

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