2007
DOI: 10.1016/j.molcel.2007.01.035
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H2B Ubiquitylation Acts as a Barrier to Ctk1 Nucleosomal Recruitment Prior to Removal by Ubp8 within a SAGA-Related Complex

Abstract: Histone modifications play an important role in transcription. We previously studied histone H2B ubiquitylation on lysine 123 and subsequent deubiquitylation by SAGA-associated Ubp8. Unlike other histone modifications, both the addition and removal of ubiquitin are required for optimal transcription. Here we report that deubiquitylation of H2B is important for recruitment of a complex containing the kinase Ctk1, resulting in phosphorylation of the RNA polymerase II (Pol II) C-terminal domain (CTD), and for sub… Show more

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Cited by 202 publications
(237 citation statements)
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“…6d), suggesting that dynamic regulation of H2Bub1 levels at promoters of dHP1c target genes plays a role in RNA pol II pausing. In this regard, work performed in yeast suggested that transcriptional activation involves sequential cycles of H2B ubiquitylation and deubiquitylation 32 and that Ubp8 promotes Ctk1-dependent phosphorylation of Ser2 in the CTD 33 , a modification that is required for activation into the elongating Pol IIo ser2 form. Nevertheless, H2Bub1 deubiquitylation at TSS does not appear to be sufficient by itself to induce pause release since dBre1 depletion, which also reduces H2Bub1 at TSS (Figs 5f and 8a), has no significant effect in pausing (Fig.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…6d), suggesting that dynamic regulation of H2Bub1 levels at promoters of dHP1c target genes plays a role in RNA pol II pausing. In this regard, work performed in yeast suggested that transcriptional activation involves sequential cycles of H2B ubiquitylation and deubiquitylation 32 and that Ubp8 promotes Ctk1-dependent phosphorylation of Ser2 in the CTD 33 , a modification that is required for activation into the elongating Pol IIo ser2 form. Nevertheless, H2Bub1 deubiquitylation at TSS does not appear to be sufficient by itself to induce pause release since dBre1 depletion, which also reduces H2Bub1 at TSS (Figs 5f and 8a), has no significant effect in pausing (Fig.…”
Section: Discussionmentioning
confidence: 99%
“…Later, during elongation, H2Bub1 extends along the entire coding region and facilitates progression of RNA pol II through chromatin. At promoters, H2Bub1 levels are dynamically regulated by Ubp8-dependent deubiquitylation 32,33 . Our results indicate that dDsk2 protects H2Bub1 against deubiquitylation by dUbp8/Nonstop and regulates the release of paused Pol IIo ser5 into productive elongation.…”
mentioning
confidence: 99%
“…The latter study provided data suggesting that SAGA DUB interacts with chromatin in a Pol II transcription‐independent manner. Studies in different eukaryotes have suggested that the presence of SAGA at the promoters of genes is needed to facilitate Pol II recruitment and pre‐initiation complex (PIC) formation (Wyce et al , 2007; Nagy et al , 2009; Helmlinger et al , 2011; Lang et al , 2011). The recruitment of SAGA and ATAC coactivator complexes to genomic loci has been suggested to take place by several distinct mechanisms: (i) by activator mediated recruitment (McMahon et al , 1998; Brown et al , 2001; Fishburn et al , 2005; Reeves & Hahn, 2005), (ii) by interactions with basal transcription machinery components (Larschan & Winston, 2001; Laprade et al , 2007; Mohibullah & Hahn, 2008) and (iii) through chromatin‐interacting domains of SAGA and ATAC subunits (Hassan et al , 2002; Vermeulen et al , 2010; Bian et al , 2011; Bonnet et al , 2014).…”
Section: Introductionmentioning
confidence: 99%
“…Ubp8-mediated deubiquitination of histone H2B regulates the expression of target genes by modulating the level of histone H3 lysine 4 methylation, a mark that is associated with active transcription (13). In addition, Ubp8 facilitates the recruitment of the Cterminal domain kinase (Ctk1) to target gene promoters via histone H2B deubiquitination, which facilitates the transition from transcription initiation to elongation (43).…”
mentioning
confidence: 99%