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

  1. Joanna Wysocka1,
  2. Michael P. Myers1,
  3. Carol D. Laherty2,
  4. Robert N. Eisenman2, and
  5. Winship Herr1,3
  1. 1Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA; 2Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA

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.

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Footnotes

  • 3 Corresponding author.

  • E-MAIL herr{at}cshl.edu; FAX (516) 367-6919.

  • Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.252103.

    • Received September 24, 2002.
    • Accepted February 5, 2003.
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