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

Item Type:Article
Title:Promoter-proximal CTCF binding promotes distal enhancer-dependent gene activation
Creators Name:Kubo, N. and Ishii, H. and Xiong, X. and Bianco, S. and Meitinger, F. and Hu, R. and Hocker, J.D. and Conte, M. and Gorkin, D. and Yu, M. and Li, B. and Dixon, J.R. and Hu, M. and Nicodemi, M. and Zhao, H. and Ren, B.
Abstract:The CCCTC-binding factor (CTCF) works together with the cohesin complex to drive 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 disproportionately affect genes that are bound by CTCF at the promoter and are dependent on long-distance enhancers. Disruption of promoter-proximal CTCF binding reduced both long-range enhancer-promoter contacts and transcription, which were restored by artificial tethering of CTCF to the promoter. Promoter-proximal CTCF binding is correlated with the transcription of over 2,000 genes across a diverse set of adult tissues. Taken together, the results of our study show that CTCF binding to promoters may promote long-distance enhancer-dependent transcription at specific genes in diverse cell types.
Source:Nature Structural & Molecular Biology
ISSN:1545-9993
Publisher:Nature Publishing Group
Date:4 January 2021
Official Publication:https://doi.org/10.1038/s41594-020-00539-5
PubMed:View item in PubMed

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