Promoter-proximal CTCF binding promotes distal enhancer-dependent gene activation.

Promoter-proximal CTCF binding promotes distal enhancer-dependent gene activation.
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启动子-近端CTCF结合促进远端增强子依赖基因激活。

DOI:
10.1038/s41594-020-00539-5
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发表时间:
2021-03
影响因子:
16.8
通讯作者:
Ren B
Ren B
中科院分区:
生物学1区
文献类型:
--
作者:
Kubo N;Ishii H;Xiong X;Bianco S;Meitinger F;Hu R;Hocker JD;Conte M;Gorkin D;Yu M;Li B;Dixon JR;Hu M;Nicodemi M;Zhao H;Ren B

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ccctc结合因子(CTCF)与内聚蛋白复合物一起驱动染色质环和拓扑相关结构域的形成,但其在基因调控中的作用尚未完全确定。在这里,我们研究了急性CTCF丢失对小鼠胚胎干细胞向神经前体细胞分化过程中染色质结构和转录程序的影响。我们在全基因组范围内确定了依赖CTCF的增强子-启动子接触,并发现它们不成比例地影响在启动子处与CTCF结合并依赖远距离增强子的基因。启动子-近端CTCF结合的破坏减少了远程增强子-启动子接触和转录,通过人工将CTCF拴在启动子上可以恢复。启动子-近端CTCF结合与超过2000个基因的转录相关,跨越多种成人组织。综上所述,我们的研究表明CTCF与启动子结合可能促进不同细胞类型中特定基因的长距离增强子依赖性转录。
The CCCTC-binding factor (CTCF) works together with the cohesin complex to drives the formation of chromatin loops and topologically associating domains, but its role in gene regulation has not been fully defined. Here, we investigated the effects of acute CTCF loss on chromatin architecture and transcriptional programs in mouse embryonic stem cells undergoing differentiation to neural precursor cells. We identified CTCF-dependent enhancer-promoter contacts genome-wide and found that they disproportionally affect genes that are bound by CTCF at promoter and dependent on long-distance enhancers. Disruption of promoter-proximal CTCF binding reduced both long-range enhancer-promoter contacts and transcription, which are restored by artificial tethering of CTCF to the promoter. Promoter-proximal CTCF binding is correlated with transcription of over 2,000 genes, across a diverse set of adult tissues. Taken together, our study shows that CTCF binding to promoters may promote long-distance-enhancer dependent transcription at specific genes in diverse cell types.
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