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Human Sin3 deacetylase and trithorax-related Set1/Ash2 histone H3-K4 methyltransferase are tethered together selectively by the cell-proliferation factor HCF-1.

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.

Pubmed ID: 12670868


  • Wysocka J
  • Myers MP
  • Laherty CD
  • Eisenman RN
  • Herr W


Genes & development

Publication Data

April 1, 2003

Associated Grants

  • Agency: NCI NIH HHS, Id: P01 CA 13106
  • Agency: NCI NIH HHS, Id: R01 CA 57138
  • Agency: NIGMS NIH HHS, Id: R01 GM 54598

Mesh Terms

  • Binding Sites
  • Cell Division
  • DNA-Binding Proteins
  • HeLa Cells
  • Herpes Simplex Virus Protein Vmw65
  • Histone Deacetylases
  • Histone-Lysine N-Methyltransferase
  • Host Cell Factor C1
  • Humans
  • Kinetics
  • Methyltransferases
  • Protein Methyltransferases
  • Proteins
  • Saccharomyces cerevisiae Proteins
  • Sin3 Histone Deacetylase and Corepressor Complex
  • Transcription Factors
  • Transfection