The Rtf1 component of the Paf1 transcriptional elongation complex is required for ubiquitination of histone H2B.
In yeast cells, the Rtf1 and Paf1 components of the Paf1 transcriptional elongation complex are important for recruitment of Set1, the histone H3-lysine 4 (H3-Lys4) methylase, to a highly localized domain at the 5' portion of active mRNA coding regions. Here, we show that Rtf1 is essential for global methylation of H3-Lys4 and H3-Lys79, but not H3-Lys36. This role of Rtf1 resembles that of Rad6, which mediates ubiquitination of histone H2B at lysine 123. Indeed, Rtf1 is required for H2B ubiquitination, suggesting that its effects on H3-Lys4 and H3-Lys79 methylation are an indirect consequence of its effect on H2B ubiquitination. Rtf1 is important for telomeric silencing, with loss of H3-Lys4 and H3-Lys79 methylation synergistically reducing Sir2 association with telomeric DNA. Dot1, the H3-Lys79 methylase, associates with transcriptionally active genes, but unlike the association of Set1 and Set2 (the H3-Lys36 methylase), this association is largely independent of Rtf1. We suggest that Rtf1 affects genome-wide ubiquitination of H2B by a mechanism that is distinct from its function as a transcriptional elongation factor.
Ng
Huck Hui
HH
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Dole
Sudhanshu
S
Struhl
Kevin
K
D015153:Blotting, Western; D002843:Chromatin / Q000378:metabolism; D019281:Dimerization; D004229:Dithiothreitol / Q000494:pharmacology; D017353:Gene Deletion; D020868:Gene Silencing; D006657:Histones / Q000737:chemistry* / Q000378:metabolism; D008239:Lysine / Q000737:chemistry; D008745:Methylation; D009687:Nuclear Proteins / Q000737:chemistry / Q000502:physiology*; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D012333:RNA, Messenger / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000502:physiology*; D035181:TATA-Box Binding Protein / Q000737:chemistry / Q000502:physiology*; D016615:Telomere / Q000378:metabolism / Q000648:ultrastructure; D014157:Transcription Factors / Q000737:chemistry / Q000502:physiology*; D014158:Transcription, Genetic; D025801:Ubiquitin / Q000737:chemistry*
D002843:Chromatin; D006657:Histones; D009687:Nuclear Proteins; C097698:PAF1 protein, S cerevisiae; D012333:RNA, Messenger; C107273:RTF1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D035181:TATA-Box Binding Protein; D014157:Transcription Factors; D025801:Ubiquitin; D008239:Lysine; D004229:Dithiothreitol