Trans-histone regulatory pathway in chromatin

Briggs, Scott; Xiao, Tiaojiang; Sun, Zu Wen; Caldwell, John R.; Shabanowitz, Jeffrey; Hunt, Donald F.; Allis, C. David; Strahl, Brian D.

doi:10.1038/nature00970

Cited by 479 publications

(371 citation statements)

References 11 publications

Supporting

Mentioning

354

Contrasting

Unclassified

Order By: Relevance

“…Thus, H2B ubiquitylation may also act as a switch for gene expression through trans-histone cross-talk (Briggs et al 2002;Sun and Allis 2002). Futhermore, the H2B ubiquitylation mediated by Rad6 and H2B deubiquitylation, caused by SAGA-associated Ubp8, defines the regions of active chromatin by affecting the methylation of histone H3 Lys 4 and Lys 79 (Henry et al 2003;Kao et al 2004).…”

Section: Usp21 Activates Transcription Genes and Development 45mentioning

confidence: 99%

Deubiquitylation of histone H2A activates transcriptional initiation via trans-histone cross-talk with H3K4 di- and trimethylation

Nakagawa

Kajitani²,

Togo³

et al. 2008

Genes Dev.

206

229

View full text Add to dashboard Cite

Transcriptional initiation is a key step in the control of mRNA synthesis and is intimately related to chromatin structure and histone modification. Here, we show that the ubiquitylation of H2A (ubH2A) correlates with silent chromatin and regulates transcriptional initiation. The levels of ubH2A vary during hepatocyte regeneration, and based on microarray expression data from regenerating liver, we identified USP21, a ubiquitin-specific protease that catalyzes the hydrolysis of ubH2A. When chromatin is assembled in vitro, ubH2A, but not H2A, specifically represses the di-and trimethylation of H3K4. USP21 relieves this ubH2A-specific repression. In addition, in vitro transcription analysis revealed that ubH2A represses transcriptional initiation, but not transcriptional elongation, by inhibiting H3K4 methylation. Notably, ubH2A-mediated repression was not observed when H3 Lys 4 was changed to arginine. Furthermore, overexpression of USP21 in the liver up-regulates a gene that is normally down-regulated during hepatocyte regeneration. Our studies revealed a novel mode of trans-histone cross-talk, in which H2A ubiquitylation controls the di-and trimethylation of H3K4, resulting in regulation of transcriptional initiation.[Keywords: Nucleosome; ubiquitylation; histone code; transcription; USP21; H2A] Supplemental material is available at http://www.genesdev.org.

show abstract

Section: Usp21 Activates Transcription Genes and Development 45mentioning

confidence: 99%

Deubiquitylation of histone H2A activates transcriptional initiation via trans-histone cross-talk with H3K4 di- and trimethylation

Nakagawa

Kajitani²,

Togo³

et al. 2008

Genes Dev.

206

229

View full text Add to dashboard Cite

show abstract

“…One well-known example of histone crosstalk in trans is the requirement of H2B C terminus monoubiquitylation (H2B monoubiquitylation, H2Bub1) for the multiple methylations of H3K4 and H3K79 (Dover et al 2002;Sun and Allis 2002;Shahbazian et al 2005), which is evolutionarily conserved from yeast to human. In Saccharomyces cerevisiae, monoubiquitylation of lysine residue 123 in histone H2B was shown to play a positive role in H3K4 and H3K79 methylations, which are involved in transcription initiation and elongation, respectively (Briggs et al 2002;Sun and Allis 2002). In mammals, H2Bub1 coupled to RAD6-mediated transcription has been reported to directly stimulate H3K4 methylation ), and synthetically ubiquitylated H2B stimulates DOT1L-mediated H3K79 methylations in vitro (McGinty et al 2008;Kim et al 2009;Oh et al 2010).…”

mentioning

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.

View full text Add to dashboard Cite

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.

show abstract

“…H2B monoubiquitylation is also a prerequisite for other histone modifications that mark active genes. Ubiquitylation of H2B K123 by the Rad6-Bre1 ubiquitin conjugase-ligase proteins in yeast (11)(12)(13) is required for dimethylation and trimethylation of H3 K4 and K79 by the Set1/COMPASS and Dot1 methyltransferases, respectively (14)(15)(16). Histone H3 K4 dimethylation and trimethylation subsequently stimulate the recruitment and activity of histone acetyltransferase and deacetylase complexes, thereby governing histone acetylation patterns on genes (17)(18)(19)(20).…”

mentioning

confidence: 99%

Small region of Rtf1 protein can substitute for complete Paf1 complex in facilitating global histone H2B ubiquitylation in yeast

Piro

Mayekar

Warner

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Histone modifications regulate transcription by RNA polymerase II and maintain a balance between active and repressed chromatin states. The conserved Paf1 complex (Paf1C) promotes specific histone modifications during transcription elongation, but the mechanisms by which it facilitates these marks are undefined. We previously identified a 90-amino acid region within the Rtf1 subunit of Paf1C that is necessary for Paf1C-dependent histone modifications in Saccharomyces cerevisiae. Here we show that this histone modification domain (HMD), when expressed as the only source of Rtf1, can promote H3 K4 and K79 methylation and H2B K123 ubiquitylation in yeast. The HMD can restore histone modifications in rtf1Δ cells whether or not it is directed to DNA by a fusion to a DNA binding domain. The HMD can facilitate histone modifications independently of other Paf1C subunits and does not bypass the requirement for Rad6-Bre1. The isolated HMD localizes to chromatin, and this interaction requires residues important for histone modification. When expressed outside the context of fulllength Rtf1, the HMD associates with and causes Paf1C-dependent histone modifications to appear at transcriptionally inactive loci, suggesting that its function has become deregulated. Finally, the Rtf1 HMDs from other species can function in yeast. Our findings suggest a direct and conserved role for Paf1C in coupling histone modifications to transcription elongation.transcription-coupled histone modifications | nucleosome I n eukaryotes, transcription occurs within the context of a restrictive, yet dynamic, chromatin environment. The posttranslational modification of histones represents a major mechanism by which cells control the structure of chromatin. Some modifications of histones include acetylation, methylation, and ubiquitylation. These modifications can alter the structural properties of nucleosomes and serve as specific effectors for the recruitment of proteins that further modify the chromatin template and regulate transcription (1).Monoubiquitylation of histone H2B on lysine (K) 123 in Saccharomyces cerevisiae is a conserved modification that is enriched on active genes but plays roles in both transcriptional repression and activation (2-4). Consistent with a repressive role, H2B monoubiquitylation stabilizes nucleosomes at yeast promoters (5), inhibits the association of the RNA polymerase (pol) II kinase Ctk1 with genes in yeast (6), and interferes with the recruitment of the elongation factor TFIIS to genes in human cells (7). In other studies, H2B monoubiquitylation has been shown to stimulate transcription of chromatin templates (8), promote nucleosome reassembly during transcription elongation (9), and inhibit chromatin compaction (10). H2B monoubiquitylation is also a prerequisite for other histone modifications that mark active genes. Ubiquitylation of H2B K123 by the Rad6-Bre1 ubiquitin conjugase-ligase proteins in yeast (11-13) is required for dimethylation and trimethylation of H3 K4 and K79 by the Set1/COMPASS and Dot1 methy...

show abstract

Trans-histone regulatory pathway in chromatin

Cited by 479 publications

References 11 publications

Deubiquitylation of histone H2A activates transcriptional initiation via trans-histone cross-talk with H3K4 di- and trimethylation

Deubiquitylation of histone H2A activates transcriptional initiation via trans-histone cross-talk with H3K4 di- and trimethylation

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

Small region of Rtf1 protein can substitute for complete Paf1 complex in facilitating global histone H2B ubiquitylation in yeast

Contact Info

Product

Resources

About