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.

NF1 microduplications: identification of seven nonrelated individuals provides further characterization of the phenotype

“…SUZ12 (also known as JJAZ1, OMIM 606245) is critical in embryonic development, 39 and OMG (OMIM 164345) is an important inhibitor of neurite overgrowth. 40 It is possible that either of these genes can contribute to phenotypes seen in NF1 microduplications, but this is yet to be explored in detail.…”

Integrated epigenomic analyses of neuronal MeCP2 reveal a role for long-range interaction with active genes

“…From each experiment, a list of mean log2 signal values was generated for all 24,275 promoters present on the array. The top 5,000 median promoter signals from the two experiments were selected on the basis of the difference between the number of promoter hits expected at random versus those observed (42). Removal of duplicate promoters yielded 4,791 and 4,798 promoter hits, respectively.…”

Regulation of Stem Cell Differentiation by Histone Methyltransferases and Demethylases

“…Supporting a role for specific transcription factors in the regulation of PcG target genes is the recent demonstration that the transcription factor Snail1 recruits the PRC2 complex to the E-cadherin promoter to repress its expression in the mesoderm of developing mouse embryos (Herranz et al 2008). Consistent with this, PcG target genes diverge when comparing different cell types (Squazzo et al 2006;Mohn et al 2008).…”

“…Comparison between cell lines such as ES, mouse embryonic fibroblast (MEF), C2C12 myoblasts, and hEF has shown that a proportion of PcG target genes are not conserved. Perhaps, not so surprisingly, PcG target genes show the largest degree of difference between normal and cancer cells (Bernstein et al 2006a;Boyer et al 2006;Bracken et al 2006;Lee et al 2006;Squazzo et al 2006;Mikkelsen et al 2007;Mohn et al 2008). This difference could be partly flawed if the cancer cells are not compared to their normal counterparts, i.e., the cell of origin for the tumor cells.…”