title: Human Sin3 deacetylase and trithorax-related Set1/Ash2 histone H3-K4 methyltransferase are tethered together selectively by the cell-proliferation factor HCF-1.
abstract: The abundant and chromatin-associated protein HCF-1 is a critical player in mammalian cell proliferation as well as herpes simplex virus (HSV) transcription. We show here that separate regions of HCF-1 critical for its role in cell proliferation associate with the Sin3 histone deacetylase (HDAC) and a previously uncharacterized human trithorax-related Set1/Ash2 histone methyltransferase (HMT). The Set1/Ash2 HMT methylates histone H3 at Lys 4 (K4), but not if the neighboring K9 residue is already methylated. HCF-1 tethers the Sin3 and Set1/Ash2 transcriptional regulatory complexes together even though they are generally associated with opposite transcriptional outcomes: repression and activation of transcription, respectively. Nevertheless, this tethering is context-dependent because the transcriptional activator VP16 selectively binds HCF-1 associated with the Set1/Ash2 HMT complex in the absence of the Sin3 HDAC complex. These results suggest that HCF-1 can broadly regulate transcription, both positively and negatively, through selective modulation of chromatin structure.
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Joanna
authors.initials: J
authors.lastname: Wysocka
authors.forename: Michael P
authors.initials: MP
authors.lastname: Myers
authors.forename: Carol D
authors.initials: CD
authors.lastname: Laherty
authors.forename: Robert N
authors.initials: RN
authors.lastname: Eisenman
authors.forename: Winship
authors.initials: W
authors.lastname: Herr
mesh_terms: D001665:Binding Sites; D002455:Cell Division / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics; D006367:HeLa Cells; D017405:Herpes Simplex Virus Protein Vmw65 / Q000378:metabolism; D006655:Histone Deacetylases / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D051863:Host Cell Factor C1; D006801:Humans; D007700:Kinetics; D008780:Methyltransferases / Q000235:genetics*; D011496:Protein Methyltransferases; D011506:Proteins / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D014157:Transcription Factors / Q000235:genetics; D014162:Transfection
chemical_list: D004268:DNA-Binding Proteins; C497692:HCFC1 protein, human; D017405:Herpes Simplex Virus Protein Vmw65; D051863:Host Cell Factor C1; D011506:Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D000076983:Histone Methyltransferases; D008780:Methyltransferases; D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C411250:SET1 protein, S cerevisiae; D006655:Histone Deacetylases; D056264:Sin3 Histone Deacetylase and Corepressor Complex