Control of cell identity genes occurs in insulated neighborhoods in mammalian chromosomes.

Control of cell identity genes occurs in insulated neighborhoods in mammalian chromosomes.
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DOI:
10.1016/j.cell.2014.09.030
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发表时间:
2014-10-09
期刊:
影响因子:
64.5
通讯作者:
Young RA
Young RA
中科院分区:
生物学1区
文献类型:
--
作者:
Dowen JM;Fan ZP;Hnisz D;Ren G;Abraham BJ;Zhang LN;Weintraub AS;Schujiers J;Lee TI;Zhao K;Young RA

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胚胎干细胞(ESC)的多能状态是通过控制细胞身份的基因的主动转录和编码谱系特异性发育调节因子的基因的抑制而产生的。在这里,我们使用ESC粘附蛋白ChIAPET数据,以确定在整个基因组的活性和抑制基因的局部染色体结构。结果产生了增强子-启动子相互作用的图谱,并揭示了超级增强子驱动的基因通常发生在由两个相互作用的CTCF位点形成的染色体结构内,所述CTCF位点由粘着素共同占据。这些环状结构形成了绝缘的邻域,其完整性对于局部基因的正确表达非常重要。我们还发现,被压抑的基因编码的谱系指定的发展调节发生在绝缘的社区。这些结果提供了新的见解细胞身份基因的转录控制和控制局部染色体结构之间的关系。
The pluripotent state of embryonic stem cells (ESCs) is produced by active transcription of genes that control cell identity and repression of genes encoding lineage-specifying developmental regulators. Here we use ESC cohesin ChIAPET data to identify the local chromosomal structures at both active and repressed genes across the genome. The results produce a map of enhancer-promoter interactions and reveal that super-enhancer driven genes generally occur within chromosome structures that are formed by the looping of two interacting CTCF sites co-occupied by cohesin. These looped structures form insulated neighborhoods whose integrity is important for proper expression of local genes. We also find that repressed genes encoding lineage-specifying developmental regulators occur within insulated neighborhoods. These results provide new insights into the relationship between transcriptional control of cell identity genes and control of local chromosome structure.
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