title: Suz12 binds to silenced regions of the genome in a cell-type-specific manner.
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.
authors.affiliation: Department of Pharmacology and the Genome Center, University of California-Davis, Davis, California 95616, USA.
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Squazzo
authors.forename: Henriette
authors.initials: H
authors.lastname: O'Geen
authors.forename: Vitalina M
authors.initials: VM
authors.lastname: Komashko
authors.forename: Sheryl R
authors.initials: SR
authors.lastname: Krig
authors.forename: Victor X
authors.initials: VX
authors.lastname: Jin
authors.forename: Sung-wook
authors.initials: SW
authors.lastname: Jang
authors.forename: Raphael
authors.initials: R
authors.lastname: Margueron
authors.forename: Danny
authors.initials: D
authors.lastname: Reinberg
authors.forename: Roland
authors.initials: R
authors.lastname: Green
authors.forename: Peggy J
authors.initials: PJ
authors.lastname: Farnham
mesh_terms: D000818:Animals; D001665:Binding Sites; D018236:Carcinoma, Embryonal / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002843:Chromatin / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D018390:Gene Targeting; D005819:Genetic Markers; D016678:Genome; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D063151:Polycomb Repressive Complex 2; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D002843:Chromatin; D005819:Genetic Markers; D006023:Glycoproteins; D018398:Homeodomain Proteins; D007136:Immunoglobulins; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D012097:Repressor Proteins; C494163:Suz12 protein, mouse; D014157:Transcription Factors; D063151:Polycomb Repressive Complex 2