2. Academic Validation
  3. SUZ12 is required for both the histone methyltransferase activity and the silencing function of the EED-EZH2 complex

SUZ12 is required for both the histone methyltransferase activity and the silencing function of the EED-EZH2 complex

  • Mol Cell. 2004 Jul 2;15(1):57-67. doi: 10.1016/j.molcel.2004.06.020.
Ru Cao 1,  Yi Zhang
Affiliations

Affiliation

  • 1 Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
PMID: 15225548 DOI: 10.1016/j.molcel.2004.06.020
Abstract

Recent studies have revealed the intrinsic Histone Methyltransferase (HMTase) activity of the EED-EZH2 complex and its role in Hox gene silencing, X inactivation, and Cancer metastasis. In this study, we focus on the function of individual components. We found that the HMTase activity requires a minimum of three components-EZH2, EED, and SUZ12-while AEBP2 is required for optimal enzymatic activity. Using a stable SUZ12 knockdown cell line, we show SUZ12 knockdown results in cell growth defects, which correlate with genome-wide alteration on H3-K27 methylation as well as upregulation of a number of Hox genes. Chromatin immunoprecipitation (ChIP) assay identified a 500 bp region located 4 kb upstream of the HoxA9 transcription initiation site as a SUZ12 binding site, which responds to SUZ12 knockdown and might play an important role in regulating HoxA9 expression. Thus, our study establishes a critical role of SUZ12 in H3-lysine 27 methylation and Hox gene silencing.

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