Histone Ubiquitylation and the Regulation of Transcription

Osley, Mary Ann; Fleming, Alastair B.; Kao, Cheng-Fu

doi:10.1007/400_006

Cited by 62 publications

(57 citation statements)

References 173 publications

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“…The N-terminal tails of histones undergo a variety of modifications such as acetylation, phosphorylation, and methylation. An additional modification, monoubiquitination, specifically on the tails of histones H2A and H2B, has been shown to play a critical role in regulating many processes within the nucleus, including transcription initiation, elongation, and silencing (Osley et al 2006;.…”

Section: Introductionmentioning

confidence: 99%

The cap binding complex influences H2B ubiquitination by facilitating splicing of the SUS1 pre-mRNA

Hossain¹,

Claggett²,

Nguyen³

et al. 2009

RNA

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Pre-messenger RNA splicing is carried out by a large ribonucleoprotein complex called the spliceosome. Despite the striking evolutionary conservation of the spliceosomal components and their functions, controversy persists about the relative importance of splicing in Saccharomyces cerevisiae-particularly given the paucity of intron-containing genes in yeast. Here we show that splicing of one pre-messenger RNA, SUS1, a component of the histone H2B ubiquitin protease machinery, is essential for establishing the proper modification state of chromatin. One protein complex that is intimately involved in premRNA splicing, the yeast cap-binding complex, appears to be particularly important, as evidenced by its extensive and unique genetic interactions with enzymes that catalyze histone H2B ubiquitination. Microarray studies show that cap binding complex (CBC) deletion has a global effect on gene expression, and for ;20% of these genes, this effect is suppressed when ubiquitination of histone H2B is eliminated. Consistent with this finding of histone H2B dependent effects on gene expression, deletion of the yeast cap binding complex leads to overubiquitination of histone H2B. A key component of the ubiquitinprotease module of the SAGA complex, Sus1, is encoded by a gene that contains two introns and is misspliced when the CBC is deleted, leading to destabilization of the ubiquitin protease complex and defective modulation of cellular H2B levels. These data demonstrate that pre-mRNA splicing plays a critical role in histone H2B ubiquitination and that the CBC in particular helps to establish the proper state of chromatin and proper expression of genes that are regulated at the level of histone H2B ubiquitination.

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Section: Introductionmentioning

confidence: 99%

The cap binding complex influences H2B ubiquitination by facilitating splicing of the SUS1 pre-mRNA

Hossain¹,

Claggett²,

Nguyen³

et al. 2009

RNA

View full text Add to dashboard Cite

show abstract

“…These modifications, including acetylation, phosphorylation, methylation, and ubiquitination of histones, have been shown to regulate transcription, chromosome condensation, and DNA repair (1,(3)(4)(5). Specific histone modifications can modify chromatin structure either directly by influencing histone-DNA and/or histone-histone interactions, as suggested in the case of histone acetylation (6), or mediate recruitment of other factors capable of modifying chromatin (7,8).…”

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confidence: 99%

“…In particular, mono-ubiquitination of H2B (ubH2B) 2 has been shown to play a crucial role in the maintenance of transcriptionally poised chromatin environment (3,21,22). Ubiquitin is transferred to H2B by the sequential action of three enzymatic activities as follows: ubiquitin activating ATPase E1, conjugating E2, and ligating E3 enzymes (23,24).…”

mentioning

confidence: 99%

HULC, a Histone H2B Ubiquitinating Complex, Modulates Heterochromatin Independent of Histone Methylation in Fission Yeast

Zofall

Grewal

2007

Journal of Biological Chemistry

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Heterochromatin in fission yeast is targeted dynamically by opposing chromatin-modifying activities capable of alleviating or promoting transcriptional gene silencing. In this study, we report the biochemical and genetic characterization of a ubiquitin-conjugating enzyme Rhp6 (a homolog of budding yeast Rad6), which has been shown to negatively affect stability of heterochromatic structures. We show that Rhp6 is a component of the multisubunit protein complex (termed HULC) that also contains two RING finger proteins Rfp1 and Rfp2, sharing homology with budding yeast Bre1 protein and a unique serinerich protein Shf1. HULC is required for ubiquitination of histone H2B at lysine 119 (H2B-K119), and it localizes to heterochromatic sequences. Moreover, our analyses suggest that Rhp6-induced changes in heterochromatic silencing are mediated predominantly through H2B ubiquitination (ubH2B), and they correlate with increased RNA polymerase II levels at repeat elements embedded within heterochromatin domains. Interestingly, heterochromatic derepression caused by Rhp6 occurs independently of the involvement of HULC subunits and ubH2B in methylation of histone H3 at lysine 4 (H3K4me). These analyses implicate ubH2B in modulation of heterochromatin, which has important implications for dynamics and many functions associated with heterochromatic structures.Histone post-translational modifications play an important role in modulating chromatin structure that underlies various chromosomal processes in eukaryotic cells (1, 2). These modifications, including acetylation, phosphorylation, methylation, and ubiquitination of histones, have been shown to regulate transcription, chromosome condensation, and DNA repair (1, 3-5). Specific histone modifications can modify chromatin structure either directly by influencing histone-DNA and/or histone-histone interactions, as suggested in the case of histone acetylation (6), or mediate recruitment of other factors capable of modifying chromatin (7,8). Factors containing interaction motifs for binding to histones methylated at specific lysine residues have been identified and shown to mediate targeting of chromatin-modifying activities implicated in either activating or repressing transcription (9 -12). For example, histone H3 methylated at lysine 9 (H3K9me) recruits conserved heterochromatin protein HP1 via its chromodomain to mediate assembly of condensed heterochromatic structures (13-15). In contrast, methylation of H3 lysine 4 (H3K4me), found at transcriptionally poised euchromatic regions, provides binding sites for PHD, chromodomain, or tudor domain-containing proteins to recruit gene activation machinery (16 -20).In addition to well studied functions of histone acetylation and methylation in modulating chromatin, histone ubiquitination has emerged as an important modification for gene regulation. In particular, mono-ubiquitination of H2B (ubH2B) 2 has been shown to play a crucial role in the maintenance of transcriptionally poised chromatin environment (3, 21, 22). Ubiquitin is tran...

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“…H2B monoubiquitylation has also been associated with silencing, underscoring the diverse roles for histone ubiquitylation in transcription. 10,11 Ubiquitylation and RNAPII Ubiquitylation and degradation of Rbp1, the largest subunit of RNAPII, was first observed as part of the The many aspects of transcription factor regulation by ubiquitin have been extensively studied, but research has often been focused on individual proteins. Yet, gene expression is generally controlled by multi-ubunit protein complexes consisting of activators, DNA-binding components and other co-factors.…”

Section: Ubiquitylation and Chromatin Reorganizationmentioning

confidence: 99%