Suz12 silences large regions of the genome in a cell type-specific manner

Department of Pharmacology and the Genome Center, University of California-Davis, Davis, California 95616, USA.
Genome Research (Impact Factor: 13.85). 08/2006; 16(7):890-900. DOI: 10.1101/gr.5306606
Source: PubMed

ABSTRACT Suz12 is a component of the Polycomb group complexes 2, 3, and 4 (PRC 2/3/4). These complexes are critical for proper embryonic development, but very few target genes have been identified in either mouse or human cells. Using a variety of ChIP-chip approaches, we have identified a large set of Suz12 target genes in five different human and mouse cell lines. Interestingly, we found that Suz12 target promoters are cell type specific, with transcription factors and homeobox proteins predominating in embryonal cells and glycoproteins and immunoglobulin-related proteins predominating in adult tumors. We have also characterized the localization of other components of the PRC complex with Suz12 and investigated the overall relationship between Suz12 binding and markers of active versus inactive chromatin, using both promoter arrays and custom tiling arrays. Surprisingly, we find that the PRC complexes can be localized to discrete binding sites or spread through large regions of the mouse and human genomes. Finally, we have shown that some Suz12 target genes are bound by OCT4 in embryonal cells and suggest that OCT4 maintains stem cell self-renewal, in part, by recruiting PRC complexes to certain genes that promote differentiation.

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Available from: Peggy J Farnham, Dec 18, 2013
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    • "EZH2 and EZH1 catalyze methylation of histone H3 lysine 27 (H3K27) and function as part of a multi-subunit complex termed Polycomb Repressive Complex 2 (PRC2) with well-documented roles in regulating cell identity (Margueron and Reinberg, 2011). PRC2 is tightly linked to the repression of transcription, whereby a variety of genes are repressed in different cell types (Squazzo et al., 2006). Chromatin-bound PRC2 mediates transcriptional repression at least in part by H3K27 methylation, although resultant chromatin architectural and mechanistic consequences are not fully understood . "
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