SUZ12 is required for both the histone methyltransferase activity and the silencing function of the EED-EZH2 complex.
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Cao R, Zhang Y
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.
- PubMed ID
- 15225548 [ View in PubMed]
- 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.