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. 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. In a variety of eukaryotic organisms, histone H3 is methylated at lysines 4, 36, and 79 (respectively H3-Lys4, H3-Lys36, H3-Lys79). In the budding yeast Saccharomyces cerevisiae, H3-Lys4 is methylated by Set1 (1Briggs S.D. Bryk M. Strahl B.D. Cheung W.L. Davie J.K. Dent S.Y. Winston F. Allis C.D. Genes Dev. 2001; 15: 3286-3295Crossref PubMed Scopus (477) Google Scholar, 2Roguev A. Schaft D. Shevchenko A. Pijnappel W.W. Wilm M. Aasland R. Stewart A.F. EMBO J. 2001; 20: 7137-7148Crossref PubMed Scopus (458) Google Scholar, 3Krogan N. Dover J. Khorrami S. Greenblatt J.F. Schneider J. Johnston M. Shilatifard A. J. Biol. 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Unexpectedly, genome-wide methylation of H3-Lys4 and H3-Lys79 depends on Rad6, an enzyme that mono-ubiquitinates lysine 123 of histone H2B (9Sun Z.W. Allis C.D. Nature. 2002; 418: 104-108Crossref PubMed Scopus (830) Google Scholar, 10Dover J. Schneider J. Tawiah-Boateng M.A. Wood A. Dean K. Johnston M. Shilatifard A. J. Biol. Chem. 2002; 277: 28368-28371Abstract Full Text Full Text PDF PubMed Scopus (425) Google Scholar, 11Ng H.H. Xu R.M. Zhang Y. Struhl K. J. Biol. Chem. 2002; 277: 34655-34657Abstract Full Text Full Text PDF PubMed Scopus (339) Google Scholar, 12Briggs S.D. Xiao T. Sun Z.-W. Caldwell J.A. Shabanowitz J. Hunt D.F. Allis C.D. Strahl B.D. Nature. 2002; 418: 498Crossref PubMed Scopus (393) Google Scholar). H3-Lys4 and H3-Lys79 methylation also depends on Bre1, an E3 ubiquitin ligase that is required for substrate selection of Rad6 (13Wood A. Krogan N.J. Dover J. Schneider J. Heidt J. Boateng M.A. Dean K. Golshani A. Zhang Y. Greenblatt J.F. Johnston M. Shilatifard A. Mol. Cell. 2003; 11: 267-274Abstract Full Text Full Text PDF PubMed Scopus (405) Google Scholar, 14Hwang W.W. Venkatasubrahmanyam S. Ianculescu A.G. Tong A. Boone C. Madhani H.D. Mol. Cell. 2003; 11: 261-266Abstract Full Text Full Text PDF PubMed Scopus (337) Google Scholar). The relationship between ubiquitination of H2B-Lys123 and methylation of H3 at lysines 4 and 79 is unidirectional, as the loss of H3 methylation does not influence H2B ubiquitination. Set1 and Dot1 are important for heterochromatic silencing (1Briggs S.D. Bryk M. Strahl B.D. Cheung W.L. Davie J.K. Dent S.Y. Winston F. Allis C.D. Genes Dev. 2001; 15: 3286-3295Crossref PubMed Scopus (477) Google Scholar, 3Krogan N. Dover J. Khorrami S. Greenblatt J.F. Schneider J. Johnston M. Shilatifard A. J. Biol. Chem. 2002; 277: 10753-10755Abstract Full Text Full Text PDF PubMed Scopus (317) Google Scholar, 6van Leeuwen F. Gafken P.R. Gottschling D.E. Cell. 2002; 109: 745-756Abstract Full Text Full Text PDF PubMed Scopus (668) Google Scholar, 7Ng H.H. Feng Q. Wang H. Erdjument-Bromage H. Tempst P. Zhang Y. Struhl K. Genes Dev. 2002; 16: 1518-1527Crossref PubMed Scopus (424) Google Scholar, 15Bryk M. Briggs S.D. Strahl B.D. Curcio M.J. Allis C.D. Winston F. Curr. Biol. 2002; 12: 165-170Abstract Full Text Full Text PDF PubMed Scopus (170) Google Scholar, 16Nislow C. Ray E. Pillus L. Mol. Biol. Cell. 1997; 8: 2421-2436Crossref PubMed Scopus (199) Google Scholar), whereas Set2 does not appear to play a role in this process. Dot1-mediated methylation and H3-Lys79 itself are important for association of Sir silencing proteins at telomeres, with the effects being more dramatic at telomere-distal regions than at telomere-proximal regions (6van Leeuwen F. Gafken P.R. Gottschling D.E. Cell. 2002; 109: 745-756Abstract Full Text Full Text PDF PubMed Scopus (668) Google Scholar, 7Ng H.H. Feng Q. Wang H. Erdjument-Bromage H. Tempst P. Zhang Y. Struhl K. Genes Dev. 2002; 16: 1518-1527Crossref PubMed Scopus (424) Google Scholar). It is likely, but not yet demonstrated, that Set1-mediated methylation of H3-Lys4 affects Sir protein association. Interestingly, methylation of H3-Lys4 (15Bryk M. Briggs S.D. Strahl B.D. Curcio M.J. Allis C.D. Winston F. Curr. Biol. 2002; 12: 165-170Abstract Full Text Full Text PDF PubMed Scopus (170) Google Scholar, 17Bernstein B.E. Humphrey E.L. Erlich R.L. Schneider R. Bouman P. Liu J.S. Kouzarides T. Schreiber S.L. Proc. Natl. Acad. Sci. U. S. A. 2002; 99: 8695-8700Crossref PubMed Scopus (596) Google Scholar) and H3-Lys79 (18Ng H.H. Ciccone D.N. Morshead K.B. Oettinger M.A. Struhl K. Proc. Natl. Acad. Sci. U. S. A. 2003; 100: 1820-1825Crossref PubMed Scopus (250) Google Scholar) is extremely low at heterochromatic loci, and H3-Lys79 methylation occurs at high levels in bulk chromatin (6van Leeuwen F. Gafken P.R. Gottschling D.E. Cell. 2002; 109: 745-756Abstract Full Text Full Text PDF PubMed Scopus (668) Google Scholar). These observations suggest that Sir proteins preferentially associate with nucleosomes that are unmethylated at H3-Lys79 (6van Leeuwen F. Gafken P.R. Gottschling D.E. Cell. 2002; 109: 745-756Abstract Full Text Full Text PDF PubMed Scopus (668) Google Scholar, 18Ng H.H. Ciccone D.N. Morshead K.B. Oettinger M.A. Struhl K. Proc. Natl. Acad. Sci. U. S. A. 2003; 100: 1820-1825Crossref PubMed Scopus (250) Google Scholar) and that Sir proteins block the ability of Dot1 to methylate H3-Lys79 (18Ng H.H. Ciccone D.N. Morshead K.B. Oettinger M.A. Struhl K. Proc. Natl. Acad. Sci. U. S. A. 2003; 100: 1820-1825Crossref PubMed Scopus (250) Google Scholar). In addition to its role in heterochromatin silencing, Set1 has an important role in transcriptional elongation. Set1 mediates both di- and trimethylation of H3-Lys4, and trimethylation correlates with transcriptional activity (19Santos-Rosa H. Schneider R. Bannister A.J. Sherriff J. Bernstein B.E. Emre N.C. Schreiber S.L. Mellor J. Kouzarides T. Nature. 2002; 419: 407-411Crossref PubMed Scopus (1603) Google Scholar). Set1 is specifically recruited by elongating RNA polymerase II (pol II) 1The abbreviation used is: pol II, polymerase II. to a highly localized domain at the 5′ region of actively transcribed genes, thereby generating a highly localized domain of trimethylated H3-Lys4 (20Ng H.H. Robert F. Young R.A. Struhl K. Mol. Cell. 2003; 11: 709-719Abstract Full Text Full Text PDF PubMed Scopus (855) Google Scholar). Recruitment of Set1 depends on some, but not all, components of the Paf1 complex (20Ng H.H. Robert F. Young R.A. Struhl K. Mol. Cell. 2003; 11: 709-719Abstract Full Text Full Text PDF PubMed Scopus (855) Google Scholar, 21Krogan N.J. Dover J. Wood A. Schneider J. Heidt J. Boateng M.A. Dean K. Ryan O.W. Golshani A. Johnston M. Greenblatt J.F. Shilatifard A. Mol. 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The Paf1 complex is also required for recruitment of Set2 and elevated levels of H3-Lys36 methylation within mRNA coding regions of transcriptionally active genes (27Krogan N.J. Kim M. Tong A. Golshani A. Cagney G. Canadien V. Richards D.P. Beattie B.K. Emili A. Boone C. Shilatifard A. Buratowski S. Greenblatt J.F. Mol. Cell. Biol. 2003; 23: 4207-4218Crossref PubMed Scopus (516) Google Scholar). Here, we show that the Rtf1 component of the Paf1 complex is required for global dimethylation of H3-Lys4 and H3-Lys79,a result obtained independently (21Krogan N.J. Dover J. Wood A. Schneider J. Heidt J. Boateng M.A. Dean K. Ryan O.W. Golshani A. Johnston M. Greenblatt J.F. Shilatifard A. Mol. Cell. 2003; 11: 721-729Abstract Full Text Full Text PDF PubMed Scopus (568) Google Scholar). Furthermore, we show that Rtf1 is required for ubiquitination of bulk H2B, strongly suggesting that Rtf1 affects H3-Lys4 and H3-Lys79 methylation through its effect on H2B ubiquitination. Rtf1 is required for silencing, and H3-Lys4 and H3-Lys79 act synergistically for stability of Sir2 at the telomeres. Dot1 is also recruited to transcriptionally active mRNA coding regions, but unlike Set1 and Set2, this recruitment 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. Yeast Strains and Plasmids—Most experiments used strain UCC1111 (28Kelly T.J. Qin S. Gottschling D.E. Parthun M.R. Mol. Cell. Biol. 2000; 20: 7051-7058Crossref PubMed Scopus (114) Google Scholar), and derivatives containing rtf1::KanR, dot1::KanR and set1::HIS5 deletion alleles that were generated by PCR-based gene replacement (29Longtine M.S. McKenzie A. Demarini D.J. Shah N.G. Wach A. Brachat A. Philippsen P. J.R. PubMed Scopus Google Scholar). which the of the of H2B, from the H2B in the of H.H. Xu R.M. Zhang Y. Struhl K. J. Biol. 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Zhang Y. Struhl K. J. Biol. Chem. 2002; 277: 34655-34657Abstract Full Text Full Text PDF PubMed Scopus (339) Google Scholar, M. Struhl K. Mol. Cell. 2002; 9: Full Text Full Text PDF PubMed Scopus Google Scholar). chromatin with by with a the and the and by in (18Ng H.H. Ciccone D.N. Morshead K.B. Oettinger M.A. Struhl K. Proc. Natl. Acad. Sci. U. S. A. 2003; 100: 1820-1825Crossref PubMed Scopus (250) Google Scholar). Sir2 and Dot1 are in that are to the the of to that of the with a of being the Rtf1 for of H3-Lys4 and H3-Lys79, but we that Set1 recruitment to mRNA coding regions in and deletion is of the bulk H3-Lys4 trimethylation is (20Ng H.H. Robert F. Young R.A. Struhl K. Mol. Cell. 2003; 11: 709-719Abstract Full Text Full Text PDF PubMed Scopus (855) Google Scholar). This the that the Paf1 complex has a more effect on methylation of histone on bulk that loss of Rtf1 H3-Lys4 and H3-Lys79, whereas has effect on H3-Lys36 methylation of H3 and this observations were for the and of the Paf1 complex (21Krogan N.J. Dover J. Wood A. Schneider J. Heidt J. Boateng M.A. Dean K. Ryan O.W. Golshani A. Johnston M. Greenblatt J.F. Shilatifard A. Mol. Cell. 2003; 11: 721-729Abstract Full Text Full Text PDF PubMed Scopus (568) Google Scholar). Interestingly, levels of trimethylated H3-Lys4, H3-Lys4, and H3-Lys79 are in the and components of the Paf1 complex (20Ng H.H. Robert F. Young R.A. Struhl K. Mol. Cell. 2003; 11: 709-719Abstract Full Text Full Text PDF PubMed Scopus (855) Google Scholar, 21Krogan N.J. Dover J. Wood A. Schneider J. Heidt J. Boateng M.A. Dean K. Ryan O.W. Golshani A. Johnston M. Greenblatt J.F. Shilatifard A. Mol. Cell. 2003; 11: 721-729Abstract Full Text Full Text PDF PubMed Scopus (568) Google Scholar). Rtf1 for H2B of H2B-Lys123 is required for genome-wide methylation of H3-Lys4 and H3-Lys79 (9Sun Z.W. Allis C.D. Nature. 2002; 418: 104-108Crossref PubMed Scopus (830) Google Scholar, 10Dover J. Schneider J. Tawiah-Boateng M.A. Wood A. Dean K. Johnston M. Shilatifard A. J. Biol. Chem. 2002; 277: 28368-28371Abstract Full Text Full Text PDF PubMed Scopus (425) Google Scholar, 11Ng H.H. Xu R.M. Zhang Y. Struhl K. J. Biol. Chem. 2002; 277: 34655-34657Abstract Full Text Full Text PDF PubMed Scopus (339) Google Scholar, 12Briggs S.D. Xiao T. Sun Z.-W. Caldwell J.A. Shabanowitz J. Hunt D.F. Allis C.D. Strahl B.D. Nature. 2002; 418: 498Crossref PubMed Scopus (393) Google Scholar, A. Krogan N.J. Dover J. Schneider J. Heidt J. Boateng M.A. Dean K. Golshani A. Zhang Y. Greenblatt J.F. Johnston M. Shilatifard A. Mol. Cell. 2003; 11: 267-274Abstract Full Text Full Text PDF PubMed Scopus (405) Google Scholar, 14Hwang W.W. Venkatasubrahmanyam S. Ianculescu A.G. Tong A. Boone C. Madhani H.D. Mol. Cell. 2003; 11: 261-266Abstract Full Text Full Text PDF PubMed Scopus (337) Google Scholar). This the that Rtf1 ubiquitination of which in for the to methylation of H3-Lys4 and of and deletion containing H2B that the of H2B is in the strain The levels of and mRNA are not in the deletion strain the that Rtf1 affects the of the that H2B ubiquitination. Rtf1 is required for H2B ubiquitination. Rtf1 for of H3-Lys4, methylation of H3-Lys79, and ubiquitination of are important for telomeric silencing, Dot1 (6van Leeuwen F. Gafken P.R. Gottschling D.E. Cell. 2002; 109: 745-756Abstract Full Text Full Text PDF PubMed Scopus (668) Google Scholar, 7Ng H.H. Feng Q. Wang H. Erdjument-Bromage H. Tempst P. Zhang Y. Struhl K. Genes Dev. 2002; 16: 1518-1527Crossref PubMed Scopus (424) Google Scholar), Set1 (1Briggs S.D. Bryk M. Strahl B.D. Cheung W.L. Davie J.K. Dent S.Y. Winston F. Allis C.D. Genes Dev. 2001; 15: 3286-3295Crossref PubMed Scopus (477) Google Scholar, 3Krogan N. Dover J. Khorrami S. Greenblatt J.F. Schneider J. Johnston M. Shilatifard A. J. Biol. Chem. 2002; 277: 10753-10755Abstract Full Text Full Text PDF PubMed Scopus (317) Google Scholar, 15Bryk M. Briggs S.D. Strahl B.D. Curcio M.J. Allis C.D. Winston F. Curr. Biol. 2002; 12: 165-170Abstract Full Text Full Text PDF PubMed Scopus (170) Google Scholar, 16Nislow C. Ray E. Pillus L. Mol. Biol. Cell. 1997; 8: 2421-2436Crossref PubMed Scopus (199) Google Scholar), Rad6 (9Sun Z.W. Allis C.D. Nature. 2002; 418: 104-108Crossref PubMed Scopus (830) Google Scholar, H. A. Gottschling D.E. L. Mol. Cell. Biol. 1997; PubMed Scopus Google Scholar), and (13Wood A. Krogan N.J. Dover J. Schneider J. Heidt J. Boateng M.A. Dean K. Golshani A. Zhang Y. Greenblatt J.F. Johnston M. Shilatifard A. Mol. Cell. 2003; 11: 267-274Abstract Full Text Full Text PDF PubMed Scopus (405) Google Scholar) are in telomeric Rtf1 is essential for H2B ubiquitination, and for methylation of H3-Lys4 and H3-Lys79, important for telomeric Indeed, in a telomeric silencing in which the gene is within the telomeric region D.E. Cell. Full Text PDF PubMed Scopus Google Scholar), show in the of that loss of Rtf1 telomeric were the (21Krogan N.J. Dover J. Wood A. Schneider J. Heidt J. Boateng M.A. Dean K. Ryan O.W. Golshani A. Johnston M. Greenblatt J.F. Shilatifard A. Mol. Cell. 2003; 11: 721-729Abstract Full Text Full Text PDF PubMed Scopus (568) Google Scholar). H3-Lys4 and H3-Lys79 Sir at methylation and H3-Lys79 itself are important for association of Sir silencing proteins at telomeric regions (6van Leeuwen F. Gafken P.R. Gottschling D.E. Cell. 2002; 109: 745-756Abstract Full Text Full Text PDF PubMed Scopus (668) Google Scholar, 7Ng H.H. Feng Q. Wang H. Erdjument-Bromage H. Tempst P. Zhang Y. Struhl K. Genes Dev. 2002; 16: 1518-1527Crossref PubMed Scopus (424) Google Scholar). the in Sir protein association in is at the itself and more at a region from the H.H. Feng Q. Wang H. Erdjument-Bromage H. Tempst P. Zhang Y. Struhl K. Genes Dev. 2002; 16: 1518-1527Crossref PubMed Scopus (424) Google Scholar). This is to the that Sir proteins are recruited to the by whereas Sir protein association at telomere-distal regions is through with M. Cell. Full Text Full Text PDF PubMed Scopus (250) Google Scholar). with H3-Lys79, loss of Set1-mediated H3-Lys4 methylation in a in Sir2 at the telomeres. In Sir2 association at the is in the strain that H3-Lys4 and H3-Lys79 methylation synergistically affects the association of silencing proteins at heterochromatic in Sir2 at the is in the suggesting that the Paf1 complex and H2B ubiquitination Sir protein association by of effects on H3 observations suggest that Sir proteins preferentially associate with nucleosomes that are unmethylated at H3-Lys79 (6van Leeuwen F. Gafken P.R. Gottschling D.E. Cell. 2002; 109: 745-756Abstract Full Text Full Text PDF PubMed Scopus (668) Google Scholar, 18Ng H.H. Ciccone D.N. Morshead K.B. Oettinger M.A. Struhl K. Proc. Natl. Acad. Sci. U. S. A. 2003; 100: 1820-1825Crossref PubMed Scopus (250) Google Scholar). The effects of and suggest that Sir proteins preferentially associate with nucleosomes in which H3 is unmethylated at both and for the of H3-Lys4 and H3-Lys79 in heterochromatic silencing, and suggest that as for H3-Lys79 (18Ng H.H. Ciccone D.N. Morshead K.B. Oettinger M.A. Struhl K. Proc. Natl. Acad. Sci. U. S. A. 2003; 100: 1820-1825Crossref PubMed Scopus (250) Google Scholar) also to Set1-mediated methylation of the H3-Lys4 and H3-Lys79 Rtf1 and ubiquitination of H2B the stability of the and to Dot1 with Genes in an Set1 and Set2 histone associate with transcriptionally active genes in an (20Ng H.H. Robert F. Young R.A. Struhl K. Mol. Cell. 2003; 11: 709-719Abstract Full Text Full Text PDF PubMed Scopus (855) Google Scholar, 21Krogan N.J. Dover J. Wood A. Schneider J. Heidt J. Boateng M.A. Dean K. Ryan O.W. Golshani A. Johnston M. Greenblatt J.F. Shilatifard A. Mol. Cell. 2003; 11: 721-729Abstract Full Text Full Text PDF PubMed Scopus (568) Google Scholar, N.J. Kim M. Tong A. Golshani A. Cagney G. Canadien V. Richards D.P. Beattie B.K. Emili A. Boone C. Shilatifard A. Buratowski S. Greenblatt J.F. Mol. Cell. Biol. 2003; 23: 4207-4218Crossref PubMed Scopus (516) Google Scholar, T. H. Y. Strahl B.D. Genes Dev. 2003; PubMed Scopus Google Scholar). Rtf1 is required for methylation of H3-Lys79, we Dot1 also associates with active genes in Dot1 associates with the and coding regions, but not with the In Dot1 association with the coding region occurs the gene is transcriptionally active but not is In Dot1 association is the but with Set1 and Set2 histone the association of Dot1 with transcriptionally active genes strongly that Dot1 with the elongating Pol II Rtf1 is largely for Dot1 recruitment to active genes, the of Dot1 association in an deletion strain in with the strain Rtf1 is extremely important for global H3-Lys79 a role in recruitment of Dot1 to active coding regions. Rtf1 of H2B and of H3-Lys4 and is that genome-wide H3-Lys4 and H3-Lys79 methylation is not by but is a consequence of global ubiquitination. H3-Lys4 H3-Lys4 dimethylation is over the entire for heterochromatic in a that is to transcriptional activity and to recruitment of Set1 to mRNA coding regions (20Ng H.H. Robert F. Young R.A. Struhl K. Mol. Cell. 2003; 11: 709-719Abstract Full Text Full Text PDF PubMed Scopus (855) Google Scholar). Furthermore, loss of Rad6, and H2B ubiquitination, H3-Lys4 methylation at active mRNA coding regions has effect on the recruitment of Set1 histone (20Ng H.H. Robert F. Young R.A. Struhl K. Mol. Cell. 2003; 11: 709-719Abstract Full Text Full Text PDF PubMed Scopus (855) Google Scholar). H3-Lys79 methylation also occurs at a over regions of the (18Ng H.H. Ciccone D.N. Morshead K.B. Oettinger M.A. Struhl K. Proc. Natl. Acad. Sci. U. S. A. 2003; 100: 1820-1825Crossref PubMed Scopus (250) Google Scholar), and the of H3-Lys79 and H2B-Lys123 within the that Dot1 activity in on H2B H.H. Xu R.M. Zhang Y. Struhl K. J. Biol. Chem. 2002; 277: 34655-34657Abstract Full Text Full Text PDF PubMed Scopus (339) Google Scholar). methylate but not nucleosomes H.H. Xu R.M. Zhang Y. Struhl K. J. Biol. 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Cell. 2003; 11: 721-729Abstract Full Text Full Text PDF PubMed Scopus (568) Google Scholar), Rtf1 is for Set2 recruitment and elevated H3-Lys36 methylation at transcriptionally active genes (27Krogan N.J. Kim M. Tong A. Golshani A. Cagney G. Canadien V. Richards D.P. Beattie B.K. Emili A. Boone C. Shilatifard A. Buratowski S. Greenblatt J.F. Mol. Cell. Biol. 2003; 23: 4207-4218Crossref PubMed Scopus (516) Google Scholar). Rtf1 is essential for genome-wide methylation of H3-Lys79 (21Krogan N.J. Dover J. Wood A. Schneider J. Heidt J. Boateng M.A. Dean K. Ryan O.W. Golshani A. Johnston M. Greenblatt J.F. Shilatifard A. Mol. Cell. 2003; 11: 721-729Abstract Full Text Full Text PDF PubMed Scopus (568) Google Scholar), but a role in recruitment of Dot1 to active genes unlike Rtf1 association with active coding regions, the Rad6 and H2B ubiquitination are recruited to regions in an (13Wood A. Krogan N.J. Dover J. Schneider J. Heidt J. Boateng M.A. Dean K. Golshani A. Zhang Y. Greenblatt J.F. 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Schneider J. Heidt J. Boateng M.A. Dean K. Ryan O.W. Golshani A. Johnston M. Greenblatt J.F. Shilatifard A. Mol. Cell. 2003; 11: 721-729Abstract Full Text Full Text PDF PubMed Scopus (568) Google Scholar). In the and components of the Paf1 complex not methylation of that also not H2B ubiquitination. the mechanism to an between components of the Paf1 complex and global ubiquitination of We for Sir2 and Shilatifard for of to

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