Effects of histone H2B ubiquitylation on the nucleosome structure and dynamics

Krajewski, Władysław; Li, Jiabin; Dou, Yali

doi:10.1093/nar/gky526

Cited by 37 publications

(43 citation statements)

References 96 publications

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“…In this study, we performed in vitro assays with the nucleosomes without histone modifications. Some histone modifications reportedly affect the nucleosome stability 58,59 . It is intriguing to study the relationship between histone modifications and RNA-mediated nucleosome destabilization.…”

Section: Discussionmentioning

confidence: 99%

Nucleosome destabilization by nuclear non-coding RNAs

et al. 2020

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In the nucleus, genomic DNA is wrapped around histone octamers to form nucleosomes. In principle, nucleosomes are substantial barriers to transcriptional activities. Nuclear noncoding RNAs (ncRNAs) are proposed to function in chromatin conformation modulation and transcriptional regulation. However, it remains unclear how ncRNAs affect the nucleosome structure. Eleanors are clusters of ncRNAs that accumulate around the estrogen receptor-α (ESR1) gene locus in long-term estrogen deprivation (LTED) breast cancer cells, and markedly enhance the transcription of the ESR1 gene. Here we detected nucleosome depletion around the transcription site of Eleanor2, the most highly expressed Eleanor in the LTED cells. We found that the purified Eleanor2 RNA fragment drastically destabilized the nucleosome in vitro. This activity was also exerted by other ncRNAs, but not by poly(U) RNA or DNA. The RNA-mediated nucleosome destabilization may be a common feature among natural nuclear RNAs, and may function in transcription regulation in chromatin.

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Section: Discussionmentioning

confidence: 99%

Nucleosome destabilization by nuclear non-coding RNAs

et al. 2020

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“…Furthermore, these results add another layer of complexity to the cross-talk, where H2B ubiquitination regulates the DOT1L-mediated nucleosome destabilization in addition to histone H3 Lys79 methylation. As previous works showed that H2B ubiquitination plays important roles in transcription elongation and nucleosome dynamics, DOT1L-mediated DNA unwrapping might facilitate this process (Wu et al 2014;Krajewski et al 2018;Lee et al 2018). At this moment, it is not clear how DOT1L binding induces the detachment of DNA with the concomitant disorder of the parts of histones.…”

Section: Dot1l Binding Destabilizes the Nucleosome Structurementioning

confidence: 93%

Structural basis of recognition and destabilization of the histone H2B ubiquitinated nucleosome by the DOT1L histone H3 Lys79 methyltransferase

et al. 2019

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DOT1L is a histone H3 Lys79 methyltransferase whose activity is stimulated by histone H2B Lys120 ubiquitination, suggesting cross-talk between histone H3 methylation and H2B ubiquitination. Here, we present cryo-EM structures of DOT1L complexes with unmodified or H2B ubiquitinated nucleosomes, showing that DOT1L recognizes H2B ubiquitin and the H2A/H2B acidic patch through a C-terminal hydrophobic helix and an arginine anchor in DOT1L, respectively. Furthermore, the structures combined with single-molecule FRET experiments show that H2B ubiquitination enhances a noncatalytic function of the DOT1L-destabilizing nucleosome. These results establish the molecular basis of the cross-talk between H2B ubiquitination and H3 Lys79 methylation as well as nucleosome destabilization by DOT1L.

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“…H2B ubiquitylation may also directly regulate transcription elongation by changing the chromatin structure. Although the role of H2B ubiquitylation in nucleosome stabilization seems to suggest the opposite effect 97 , 98 , several biochemical studies have shown that H2B ubiquitylation disrupts chromatin compaction and promotes an open chromatin structure 99 – 101 . H2B deubiquitylation has also been shown to have a profound effect on subsequent H3 methylation and productive transcription 14 , 15 , 88 , 89 , 102 , 103 .…”

Section: Functional Modules Of Sagamentioning

confidence: 99%

Dynamic modules of the coactivator SAGA in eukaryotic transcription

et al. 2020

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SAGA (Spt-Ada-Gcn5 acetyltransferase) is a highly conserved transcriptional coactivator that consists of four functionally independent modules. Its two distinct enzymatic activities, histone acetylation and deubiquitylation, establish specific epigenetic patterns on chromatin and thereby regulate gene expression. Whereas earlier studies emphasized the importance of SAGA in regulating global transcription, more recent reports have indicated that SAGA is involved in other aspects of gene expression and thus plays a more comprehensive role in regulating the overall process. Here, we discuss recent structural and functional studies of each SAGA module and compare the subunit compositions of SAGA with related complexes in yeast and metazoans. We discuss the regulatory role of the SAGA deubiquitylating module (DUBm) in mRNA surveillance and export, and in transcription initiation and elongation. The findings suggest that SAGA plays numerous roles in multiple stages of transcription. Further, we describe how SAGA is related to human disease. Overall, in this report, we illustrate the newly revealed understanding of SAGA in transcription regulation and disease implications for fine-tuning gene expression.

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Effects of histone H2B ubiquitylation on the nucleosome structure and dynamics

Cited by 37 publications

References 96 publications

Nucleosome destabilization by nuclear non-coding RNAs

Nucleosome destabilization by nuclear non-coding RNAs

Structural basis of recognition and destabilization of the histone H2B ubiquitinated nucleosome by the DOT1L histone H3 Lys79 methyltransferase

Dynamic modules of the coactivator SAGA in eukaryotic transcription

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