Suz12 binds to silenced regions of the genome in a cell-type-specific manner
Suz12 binds to silenced regions of the genome in a cell-type-specific manner
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DOI：
10.1101/gr.5306606
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发表时间：
2006-07-01
期刊：
影响因子：
7
通讯作者：
Farnham, Peggy J.
中科院分区：
文献类型：
--
作者：
Squazzo, Sharon L.;O'Geen, Henriette;Farnham, Peggy J.
Suzl 2是Polycomb族络合物2、3和4（PRC 2/ 3/ 4）的组分。这些复合物对胚胎的正常发育至关重要，但在小鼠或人类细胞中发现的靶基因很少。使用各种ChIP芯片方法，我们已经在五种不同的人类和小鼠细胞系中鉴定了一大组Suz 12靶基因。有趣的是，我们发现Suz 12靶启动子是细胞类型特异性的，其中转录因子和同源框蛋白在胚胎细胞中占主导地位，糖蛋白和免疫球蛋白相关蛋白在成人肿瘤中占主导地位。我们还表征了PRC复合物的其他组分与Suz 12的定位，并使用启动子阵列和定制平铺阵列研究了Suz 12结合与活性与非活性染色质标记之间的总体关系。令人惊讶的是，我们发现PRC复合物可以定位到离散的结合位点或通过小鼠和人类基因组的大区域传播。最后，我们已经表明，一些Suz 12的靶基因被OCT 4结合在胚胎细胞中，并表明OCT 4维持干细胞自我更新，部分是通过招募PRC复合物到某些促进分化的基因。
Suzl2 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.