Dynamic Rewiring of Promoter-Anchored Chromatin Loops during Adipocyte Differentiation
Dynamic Rewiring of Promoter-Anchored Chromatin Loops during Adipocyte Differentiation
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DOI：
10.1016/j.molcel.2017.04.010
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发表时间：
2017-05-04
期刊：
影响因子：
16
通讯作者：
Mandrup, Susanne
中科院分区：
文献类型：
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作者：
Siersbaek, Rasmus;Madsen, Jesper Grud Skat;Mandrup, Susanne
转录启动子及其末端调控元件之间的相互作用在转录调控中起着重要作用；然而，这些相互作用在多大程度上受到信号的快速调节尚不清楚。在这里，我们使用启动子捕获Hi-C来证明在诱导3T3-L1前脂肪细胞分化后的4小时内快速重组启动子锚定的染色质环。新的启动子-增强子环的建立与组蛋白H3赖氨酸4单甲基化和二甲基化增强子的激活紧密相连，组蛋白H3赖氨酸27乙酰化的获得、MED1、SMC1和P300蛋白与这些区域的结合以及靶基因的激活证明了这一点。有趣的是，连接激活的增强子和启动子的环的形成也与NCoR和HDAC等辅阻遏子的广泛招募有关，这表明这类辅调控子可能在增强子激活过程中发挥以前未被认识到的作用。
Interactions between transcriptional promoters and their distal regulatory elements play an important role in transcriptional regulation; however, the extent to which these interactions are subject to rapid modulations in response to signals is unknown. Here, we use promoter capture Hi-C to demonstrate a rapid reorganization of promoter-anchored chromatin loops within 4 hr after inducing differentiation of 3T3-L1 preadipocytes. The establishment of new promoter-enhancer loops is tightly coupled to activation of poised (histone H3 lysine 4 mono-and dimethylated) enhancers, as evidenced by the acquisition of histone H3 lysine 27 acetylation and the binding of MED1, SMC1, and P300 proteins to these regions, as well as to activation of target genes. Intriguingly, formation of loops connecting activated enhancers and promoters is also associated with extensive recruitment of corepressors such as NCoR and HDACs, indicating that this class of coregulators may play a previously unrecognized role during enhancer activation.