Histone Crosstalk between H2B Monoubiquitination and H3 Methylation Mediated by COMPASS

Lee, Jung Shin; Shukla, Abhijit; Schneider, Jessica; Swanson, Selene K.; Washburn, Michael P.; Florens, Laurence; Bhaumik, Sukesh R.; Shilatifard, Ali

doi:10.1016/j.cell.2007.09.046

Cited by 373 publications

(361 citation statements)

References 60 publications

Supporting

Mentioning

347

Contrasting

Unclassified

Order By: Relevance

“…Notably, H2B monoubiquitylation was subsequently found to be required for di-and trimethylation of lysine 4 and lysine 79 of histone H3 at transcribed chromatin [42][43][44][45][46][47][48]. This pathway is conserved from yeast to mammals, and is dependent on a host of additional proteins that converge at the elongating RNA Pol II [41,[49][50][51][52][53][54]. Subsequently, the mammalian orthologs of the yeast Bre1, RNF20 and RNF40, were identified [55,56].…”

Section: Open Access Under CC By-nc-nd Licensementioning

confidence: 99%

“…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%

See 1 more Smart Citation

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

et al. 2011

View full text Add to dashboard Cite

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...

show abstract

Section: Open Access Under CC By-nc-nd Licensementioning

confidence: 99%

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

View full text Add to dashboard Cite

show abstract

“…Wdr82 interacts with serine 5-phosphorylated C-terminal domain repeats of RNA polymerase II and recruits the Setd1a complex to the transcriptional start sites of active genes [41]. Further, mono-ubiquitination of histone H2B is required for association of the yeast analog of Wdr82 (Cps35) to chromatin and the subsequent tri-methylation of histone H3K4 [42].…”

Section: Discussionmentioning

confidence: 99%

Efficient differentiation of murine embryonic stem cells requires the binding of CXXC finger protein 1 to DNA or methylated histone H3-Lys4

Mahadevan

Skalnik

2016

Gene

View full text Add to dashboard Cite

Mammalian CXXC finger protein 1 (Cfp1) is a DNA-binding protein that is a component of the Setd1 histone methyltransferase complexes and is a critical epigenetic regulator of both histone and cytosine methylation. Murine embryonic stem (ES) cells lacking Cfp1 exhibit a loss of histone H3-Lys4 tri-methylation (H3K4me3) at many CpG islands, and a mis-localization of this epigenetic mark to heterochromatic sub-nuclear domains.Furthermore, these cells fail to undergo cellular differentiation in vitro. These defects are rescued upon introduction of a Cfp1-expression vector. Cfp1 contains an N-terminal plant homeodomain (PHD), a motif frequently observed in chromatin associated proteins that functions as a reader module of histone marks. Here, we report that the Cfp1 PHD domain directly and specifically binds to histone H3K4me1/me2/me3 marks. Introduction of individual mutations at key Cfp1 PHD residues (Y28, D44, or W49) ablates this histone interaction both in vitro and in vivo. The W49A point mutation does not affect the ability of Cfp1 to rescue appropriate restriction of histone H3K4me3 to euchromatic subnuclear domains or in vitro cellular differentiation in Cfp1-null ES cells. Similarly, a mutated form of Cfp1 that lacks DNA-binding activity (C169A) rescues in vitro cellular differentiation. However, rescue of Cfp1-null ES cells with a double mutant form of Cfp1 (W49A, C169A) results in partially defective in vitro differentiation. These data define the Cfp1 PHD domain as a reader of histone H3K4me marks and provide evidence that this activity is involved in the regulation of lineage commitment in ES cells.

show abstract

“…6A), and we thus would assume that the core area of H3 (where K79 is in) could hardly interact with AgNPs. To this end, the low H3K79me1 level upon AgNPs could be due to the reduced level of H3K4me3 [47]; however, a direct interruption of H3K79 methylation by AgNPs could not be excluded.…”

Section: Mds Indicates Potential Binding Of Agnps To H3 and H4mentioning

confidence: 99%

“…As a marker for gene activation, H3K79me1 has a strong tie with H3K4me3 [47]. Moreover, H3K79me1 is also highly required for the activation of the coding region of the b maj -globin gene [21].…”

Section: Reduced H3k4me3 and H3k79me1 Within The B-globin Locus Upon mentioning

confidence: 99%

Silver nanoparticle-induced hemoglobin decrease involves alteration of histone 3 methylation status

Qian

Zhang

et al. 2015

Biomaterials

View full text Add to dashboard Cite

a b s t r a c tSilver nanoparticles (nanosilver, AgNPs) have been shown to induce toxicity in vitro and in vivo; however, the molecular bases underlying the detrimental effects have not been thoroughly understood. Although there are numerous studies on its genotoxicity, only a few studies have investigated the epigenetic changes, even less on the changes of histone modifications by AgNPs. In the current study, we probed the AgNP-induced alterations to histone methylation that could be responsible for globin reduction in erythroid cells. AgNP treatment caused a significant reduction of global methylation level for histone 3 (H3) in erythroid MEL cells at sublethal concentrations, devoid of oxidative stress. The ChIP-PCR analyses demonstrated that methylation of H3 at lysine (Lys) 4 (H3K4) and Lys 79 (H3K79) on the b-globin locus was greatly reduced. The reduction in methylation could be attributed to decreased histone methyltransferase DOT-1L and MLL levels as well as the direct binding between AgNPs to H3/H4 that provide steric hindrance to prevent methylation as predicted by the all-atom molecular dynamics simulations. This direct interaction was further proved by AgNP-mediated pull-down assay and immunoprecipitation assay. These changes, together with decreased RNA polymerase II activity and chromatin binding at this locus, resulted in decreased hemoglobin production. By contrast, Ag ion-treated cells showed no alterations in histone methylation level. Taken together, these results showed a novel finding in which AgNPs could alter the methylation status of histone. Our study therefore opens a new avenue to study the biological effects of AgNPs at sublethal concentrations from the perspective of epigenetic mechanisms.

show abstract

Histone Crosstalk between H2B Monoubiquitination and H3 Methylation Mediated by COMPASS

Cited by 373 publications

References 60 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

Efficient differentiation of murine embryonic stem cells requires the binding of CXXC finger protein 1 to DNA or methylated histone H3-Lys4

Silver nanoparticle-induced hemoglobin decrease involves alteration of histone 3 methylation status

Contact Info

Product

Resources

About