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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.

Genes & development | Apr 1, 2003

http://www.ncbi.nlm.nih.gov/pubmed/12670868

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 RIS Download

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

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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

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