Histone H2B Monoubiquitination Functions Cooperatively with FACT to Regulate Elongation by RNA Polymerase II

Pavri, Rushad; Zhu, Bing; Li, Guohong; Trojer, Patrick; Mandal, Subhrangsu S.; Shilatifard, Ali; Reinberg, Danny

doi:10.1016/j.cell.2006.04.029

Cited by 635 publications

(695 citation statements)

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“…Thus, while carrying out its regular enzymatic activity in the DDR context, it was presumably physically and functionally detached from its regular context. In the transcription context, H2B monoubiquitylation in yeast and mammals is dependent on the early steps in transcription initiation and elongation, and the corresponding E3 ligase closely interacts with many proteins that take part in this process, some of which associate directly with RNA Pol II [41,[49][50][51][52][53][54]99,100]. It is not entirely clear how many of the proteins surrounding RNF20-RNF40 in the transcription context accompany this heterodimer to the DNA damage sites.…”

Section: Rnf20-rnf40 Is Called To Emergency Action Upon Dna Damage Inmentioning

confidence: 99%

RNF20–RNF40: A ubiquitin‐driven link between gene expression and the DNA damage response

et al. 2011

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a b s t r a c tThe DNA damage response (DDR) is emerging as a vast signaling network that temporarily modulates numerous aspects of cellular metabolism in the face of DNA lesions, especially critical ones such as the double strand break (DSB). The DDR involves extensive dynamics of protein post-translational modifications, most notably phosphorylation and ubiquitylation. The DSB response is mobilized primarily by the ATM protein kinase, which phosphorylates a plethora of key players in its various branches. It is based on a core of proteins dedicated to the damage response, and a cadre of proteins borrowed temporarily from other cellular processes to help meet the challenge. A recently identified novel component of the DDR pathway -histone H2B monoubiquitylationexemplifies this principle. In mammalian cells, H2B monoubiquitylation is driven primarily by an E3 ubiquitin ligase composed of the two RING finger proteins RNF20 and RNF40. Generation of monoubiquitylated histone H2B (H2Bub) has been known to be coupled to gene transcription, presumably modulating chromatin decondensation at transcribed regions. New evidence indicates that the regulatory function of H2Bub on gene expression can selectively enhance or suppress the expression of distinct subsets of genes through a mechanism involving the hPAF1 complex and the TFIIS protein. This delicate regulatory process specifically affects genes that control cell growth and genome stability, and places RNF20 and RNF40 in the realm of tumor suppressor proteins. In parallel, it was found that following DSB induction, the H2B monoubiquitylation module is recruited to damage sites where it induces local H2Bub, which in turn is required for timely recruitment of DSB repair protein and, subsequently, timely DSB repair. This pathway represents a crossroads of the DDR and chromatin organization, and is a typical example of how the DDR calls to action functional modules that in unprovoked cells regulate other processes. Ó 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. The DNA damage response: borrowing functional modules in an emergencyCellular metabolism is controlled by numerous, interlocked signaling networks. These networks are constantly responding to internal and external stimuli related to the cell's normal life cycle and functions, and to threats to its well being. A major threat to cellular homeostasis is subversion of its genomic stability, which may lead to undue cell death or to neoplasia [1,2]. DNA damage caused by internal or external damaging agents is a major danger to the integrity of the cellular genome. The cellular defense system against this threat is the DNA damage response (DDR) -an elaborate signaling network activated by DNA damage, which swiftly modulates many physiological processes [3,4]. A strong trigger of the DDR is the DNA double-strand break (DSB) [5,6]. DSBs are induced by ionizing radiation, radiomimetic chemicals, reactive oxygen species formed in the course of normal metabolism, and can also result from replic...

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Section: Rnf20-rnf40 Is Called To Emergency Action Upon Dna Damage Inmentioning

confidence: 99%

RNF20–RNF40: A ubiquitin‐driven link between gene expression and the DNA damage response

et al. 2011

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“…In this regard, Fleming et al (2008) found that H2Bub1 plays specific roles in GAL1/10 gene expression in budding yeast, and these roles are independent of its regulation of H3 methylation. In addition, Pavri et al (2006) demonstrated that H2Bub1 directly stimulates FACT (FAcilitates Chromatin Transcription)-mediated transcription using an in vitro chromatin-based transcription system. The ubiquitin moiety of histone H2B is removed by the deubiquitylases, UBP8 and UBP10 (Weake and Workman 2008).…”

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confidence: 99%

H2B monoubiquitylation is a 5′-enriched active transcription mark and correlates with exon–intron structure in human cells

Jung

Kim²,

Kim³

et al. 2012

Genome Res.

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H2B monoubiquitylation (H2Bub1), which is required for multiple methylations of both H3K4 and H3K79, has been implicated in gene expression in numerous organisms ranging from yeast to human. However, the molecular crosstalk between H2Bub1 and other modifications, especially the methylations of H3K4 and H3K79, remains unclear in vertebrates. To better understand the functional role of H2Bub1, we measured genome-wide histone modification patterns in human cells. Our results suggest that H2Bub1 has dual roles, one that is H3 methylation dependent, and another that is H3 methylation independent. First, H2Bub1 is a 59-enriched active transcription mark and co-occupies with H3K79 methylations in actively transcribed regions. Second, this study shows for the first time that H2Bub1 plays a histone H3 methylationsindependent role in chromatin architecture. Furthermore, the results of this work indicate that H2Bub1 is largely positioned at the exon-intron boundaries of highly expressed exons, and it demonstrates increased occupancy in skipped exons compared with flanking exons in the human and mouse genomes. Our findings collectively suggest that a potentiating mechanism links H2Bub1 to both H3K79 methylations in actively transcribed regions and the exon-intron structure of highly expressed exons via the regulation of nucleosome dynamics during transcription elongation.

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“…FACT recruitment results in nucleosome remodeling making the H2A/B dimer accessible for BRE1A ubiquitination. FACT can in turn directly or indirectly recruit BRE1A complex (RNF20/40) facilitating ubiquitination of H2B‐Lys120 29, 30. In agreement with this, FACT is required in vivo30 for BRE1A/B localization to chromatin in DNA damage responses.…”

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confidence: 56%

Synthetic Nucleosomes Reveal that GlcNAcylation Modulates Direct Interaction with the FACT Complex

et al. 2016

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Transcriptional regulation can be established by various post‐translational modifications (PTMs) on histone proteins in the nucleosome and by nucleobase modifications on chromosomal DNA. Functional consequences of histone O‐GlcNAcylation (O‐GlcNAc=O‐linked β‐N‐acetylglucosamine) are largely unexplored. Herein, we generate homogeneously GlcNAcylated histones and nucleosomes by chemical post‐translational modification. Mass‐spectrometry‐based quantitative interaction proteomics reveals a direct interaction between GlcNAcylated nucleosomes and the “facilitates chromatin transcription” (FACT) complex. Preferential binding of FACT to GlcNAcylated nucleosomes may point towards O‐GlcNAcylation as one of the triggers for FACT‐driven transcriptional control.

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Histone H2B Monoubiquitination Functions Cooperatively with FACT to Regulate Elongation by RNA Polymerase II

Cited by 635 publications

References 65 publications

RNF20–RNF40: A ubiquitin‐driven link between gene expression and the DNA damage response

RNF20–RNF40: A ubiquitin‐driven link between gene expression and the DNA damage response

H2B monoubiquitylation is a 5′-enriched active transcription mark and correlates with exon–intron structure in human cells

Synthetic Nucleosomes Reveal that GlcNAcylation Modulates Direct Interaction with the FACT Complex

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