细胞身份基因的调控发生在哺乳动物染色体的绝缘区域。
Control of cell identity genes occurs in insulated neighborhoods in mammalian chromosomes.
作者信息
Dowen Jill M, Fan Zi Peng, Hnisz Denes, Ren Gang, Abraham Brian J, Zhang Lyndon N, Weintraub Abraham S, Schujiers Jurian, Lee Tong Ihn, Zhao Keji, Young Richard A
机构信息
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142.
Computational and Systems Biology Program.
出版信息
Cell. 2014 Oct 9;159(2):374-387. doi: 10.1016/j.cell.2014.09.030.
Abstract
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 ChIA-PET 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 insights into the relationship between transcriptional control of cell identity genes and control of local chromosome structure.
摘要
胚胎干细胞（ESC）的多能状态是由控制细胞身份的基因的活跃转录以及编码谱系特异性发育调节因子的基因的抑制所产生的。在这里，我们使用ESC黏连蛋白ChIA-PET数据来识别全基因组中活跃基因和抑制基因处的局部染色体结构。结果生成了一个增强子-启动子相互作用图谱，并揭示了超级增强子驱动的基因通常出现在由两个被黏连蛋白共同占据的相互作用的CTCF位点环化形成的染色体结构内。这些环状结构形成了绝缘邻域，其完整性对于局部基因的正确表达很重要。我们还发现，编码谱系特异性发育调节因子的抑制基因出现在绝缘邻域内。这些结果为细胞身份基因的转录控制与局部染色体结构控制之间的关系提供了见解。
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本文引用的文献
1
The 3D genome in transcriptional regulation and pluripotency.转录调控和多能性中的三维基因组
Cell Stem Cell. 2014 Jun 5;14(6):762-75. doi: 10.1016/j.stem.2014.05.017.
2
Identification of alternative topological domains in chromatin.染色质中其他拓扑结构域的鉴定。
Algorithms Mol Biol. 2014 May 3;9:14. doi: 10.1186/1748-7188-9-14. eCollection 2014.
3
A single oncogenic enhancer rearrangement causes concomitant EVI1 and GATA2 deregulation in leukemia.单一癌基因增强子重排导致白血病中 EVI1 和 GATA2 的同时失调。
Cell. 2014 Apr 10;157(2):369-381. doi: 10.1016/j.cell.2014.02.019. Epub 2014 Apr 3.
4
CTCF: an architectural protein bridging genome topology and function.CTCF：连接基因组拓扑结构和功能的结构蛋白。
Nat Rev Genet. 2014 Apr;15(4):234-46. doi: 10.1038/nrg3663. Epub 2014 Mar 11.
5
CTCF and cohesin cooperate to organize the 3D structure of the mammalian genome.CCCTC结合因子（CTCF）与黏连蛋白协同作用，共同构建哺乳动物基因组的三维结构。
Proc Natl Acad Sci U S A. 2014 Jan 21;111(3):889-90. doi: 10.1073/pnas.1321957111. Epub 2014 Jan 7.
6
NOTCH1-RBPJ complexes drive target gene expression through dynamic interactions with superenhancers.NOTCH1-RBPJ 复合物通过与超级增强子的动态相互作用驱动靶基因表达。
Proc Natl Acad Sci U S A. 2014 Jan 14;111(2):705-10. doi: 10.1073/pnas.1315023111. Epub 2013 Dec 27.
7
Interactome maps of mouse gene regulatory domains reveal basic principles of transcriptional regulation.小鼠基因调控区域互作组图谱揭示了转录调控的基本原理。
Cell. 2013 Dec 19;155(7):1507-20. doi: 10.1016/j.cell.2013.11.039.
8
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Proc Natl Acad Sci U S A. 2014 Jan 21;111(3):996-1001. doi: 10.1073/pnas.1317788111. Epub 2013 Dec 13.
9
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Stem Cell Reports. 2013 Oct 24;1(5):371-8. doi: 10.1016/j.stemcr.2013.09.002. eCollection 2013.
10
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