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

Naoki Kubo, Haruhiko Ishii, Xiong Xiong, Simona Bianco, Franz Meitinger, Rong Hu, James D. Hocker, Mattia Conte, David Gorkin, Miao Yu, Bin Li, Jesse R. Dixon, Ming Hu, Mario Nicodemi, Huimin Zhao, Bing Ren

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)152-161
Number of pages10
JournalNature Structural and Molecular Biology
Volume28
Issue number2
DOIs
Publication statusPublished - Feb 2021
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology

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