Cohesins form chromosomal cis-interactions at the developmentally regulated IFNG locus.
Cohesins form chromosomal cis-interactions at the developmentally regulated IFNG locus.
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DOI：
10.1038/nature08079
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发表时间：
2009-07-16
期刊：
影响因子：
64.8
通讯作者：
Merkenschlager, Matthias
中科院分区：
文献类型：
--
作者：
Hadjur, Suzana;Williams, Luke M.;Ryan, Natalie K.;Cobb, Bradley S.;Sexton, Tom;Fraser, Peter;Fisher, Amanda G.;Merkenschlager, Matthias
粘附素介导的姐妹染色单体凝聚力是染色体分离和复制后DNA修复所必需的。此外，来自模型生物和人类遗传学的证据表明，粘附素在基因表达控制中发挥作用。最近的研究发现，哺乳动物的粘附素复合体被招募到DNase I超敏位点(HSS)的一个子集，并被DNA结合蛋白CTCF招募到保守的非编码序列，这一非典型作用得到了合理的解释。CTCF作用于绝缘体(控制增强子和启动子之间的相互作用)和边界元件(区分不同染色质结构的区域)，而粘附素有助于CTCF的增强子阻断活性。其潜在的机制尚不清楚，粘附素的全谱功能仍有待阐明。在这里，我们表明，在发育调节的细胞因子基因座IFNG上，粘附素形成了顺式染色体中细胞类型特异的远程染色体相互作用的拓扑和机制基础。因此，粘附素限制染色体拓扑结构的能力不仅被用于姐妹染色单体凝聚，而且还被用于动态定义特定基因座的空间构象。粘附素功能的这一新方面对正常发育和疾病可能是重要的。
Cohesin-mediated sister chromatid cohesion is essential for chromosome segregation and post-replicative DNA repair. In addition, evidence from model organisms and from human genetics suggests that cohesin plays a role in the control of gene expression. This non-canonical role has recently been rationalized by the findings that mammalian cohesin complexes are recruited to a subset of DNase I hypersensitive sites (HSS) and to conserved non-coding sequences by the DNA binding protein CTCF. CTCF functions at insulators (which control interactions between enhancers and promoters) and at boundary elements (which demarcate regions of distinct chromatin structure), and cohesin contributes to CTCF’s enhancer blocking activity. The underlying mechanisms remain unknown, and the full spectrum of cohesin functions remains to be elucidated. Here we show that cohesin forms the topological and mechanistic basis for cell type-specific long-range chromosomal interactions in cis at the developmentally regulated cytokine locus IFNG. Hence, cohesin’s ability to constrain chromosome topology is utilized not only for the purpose of sister chromatid cohesion, but also to dynamically define the spatial conformation of specific loci. This novel aspect of cohesin function is likely of importance to normal development and to disease.
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影响因子：
5.4
作者：
Hewitt, SL;High, FA;Merkenschlager, M
通讯作者：
Merkenschlager, M
影响因子：
4
作者：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
Rao, A
DOI：
10.1073/pnas.0600326103
发表时间：
2006-07-11
影响因子：
11.1
作者：
Kurukuti, Sreenivasulu;Tiwari, Vijay Kumar;Ohlsson, Rolf
通讯作者：
Ohlsson, Rolf