TY - JOUR
T1 - Promoter-proximal CTCF binding promotes distal enhancer-dependent gene activation
AU - Kubo, Naoki
AU - Ishii, Haruhiko
AU - Xiong, Xiong
AU - Bianco, Simona
AU - Meitinger, Franz
AU - Hu, Rong
AU - Hocker, James D.
AU - Conte, Mattia
AU - Gorkin, David
AU - Yu, Miao
AU - Li, Bin
AU - Dixon, Jesse R.
AU - Hu, Ming
AU - Nicodemi, Mario
AU - Zhao, Huimin
AU - Ren, Bing
N1 - Funding Information:
We thank E. Nora and B. Bruneau for exchanging datasets and reagents. We would like to give special thanks to S. Kuan for operating the sequencing instruments and T. Liu and Z. Ye for helping with experiments. We would like to acknowledge the help of V. Lobanenkov and A. Desai for giving helpful advice and the help of F. Yue, X. Wang, I. Juric and A. Abnousi for sharing computational pipelines. We would also like to give special thanks to R. Raviram, R. Fang, Y. Zhang, A. Schmitt and S. Chee for sharing helpful information and protocols, as well as all of the other members of the Ren laboratory. This work was supported by the Ludwig Institute for Cancer Research (B.R.), NIH (1U54DK107977-01) (B.R.), NIH (1U54DK107965) (H.Z.), a Ruth L. Kirschstein Institutional National Research Award from the National Institute for General Medical Sciences (T32 GM008666) (J.D.H.) and a Postdoc fellowship from the TOYOBO Biotechnology Foundation (N.K.).
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2021/2
Y1 - 2021/2
N2 - 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.
AB - 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.
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U2 - 10.1038/s41594-020-00539-5
DO - 10.1038/s41594-020-00539-5
M3 - Article
C2 - 33398174
AN - SCOPUS:85098752617
VL - 28
SP - 152
EP - 161
JO - Nature Structural Biology
JF - Nature Structural Biology
SN - 1545-9993
IS - 2
ER -