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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.

Wysocka, Joanna and Myers, Michael P and Laherty, Carol D and Eisenman, Robert N and Herr, Winship (2003) 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, 17 (7). pp. 896-911. ISSN 0890-9369

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Article URL: http://genesdev.cshlp.org/content/17/7/896.full

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.

Item Type: Article
Additional Information: This article is freely available in PubMed Central and at the journal's website.
DOI: 10.1101/gad.252103
PubMed ID: 12670868
PMCID: PMC196026
Grant Numbers: R01GM 54598 , P01CA13106, R01CA57138
Keywords or MeSH Headings: Binding Sites; Cell Division/physiology; DNA-Binding Proteins/genetics; Hela Cells; Herpes Simplex Virus Protein Vmw65/metabolism; Histone Deacetylases/genetics/isolation & purification/metabolism; Histone-Lysine N-Methyltransferase; Host Cell Factor C1; Humans; Kinetics; Methyltransferases/genetics; Proteins/metabolism; Saccharomyces cerevisiae Proteins/genetics; Transcription Factors/genetics; Transfection;
Subjects: Molecules > Proteins > Transcription factors
Molecules > Chromosomes > Chromatin
Cellular and Organismal Processes > Cell Physiology > Cell proliferation
Depositing User: Library Staff
Date Deposited: 24 Nov 2008 19:54
Last Modified: 07 May 2010 21:48
URI: http://authors.fhcrc.org/id/eprint/187

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