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Published online before print June 2, 2006
Genome Research, DOI: 10.1101/gr.5306606
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Letter

Suz12 binds to silenced regions of the genome in a cell-type-specific manner

Sharon L. Squazzo1, Henriette O’Geen1, Vitalina M. Komashko1, Sheryl R. Krig1, Victor X. Jin1, Sung-wook Jang4, Raphael Margueron3, Danny Reinberg3, Roland Green2 and Peggy J. Farnham1,5

1 Department of Pharmacology and the Genome Center, University of California–Davis, Davis, California 95616, USA; 2 NimbleGen Systems Inc., Madison, Wisconsin 53711, USA; 3 Howard Hughes Medical Institute, Division of Nucleic Acids Enzymology, Department of Biochemistry, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA; 4 Graduate Program in Cellular and Molecular Biology, University of Wisconsin, Madison, Wisconsin 53706, USA

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.


5 Corresponding author.

E-mail pjfarnham{at}ucdavis.edu; fax (530) 754-9658.

Article published online before print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.5306606

[Supplemental material is available online at www.genome.org. The sequence data from this study have been submitted to GEO under accession nos. GSE4902 [NCBI GEO] , GSE4904 [NCBI GEO] , GSE4905 [NCBI GEO] , GSE4907 [NCBI GEO] , and GSE4908 [NCBI GEO] .]


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