ZNF143 mediates CTCF-bound promoter–enhancer loops required for murine hematopoietic stem and progenitor cell function

Qiling Zhou, Miao Yu, Roberto Tirado-Magallanes, Bin Li, Lingshi Kong, Mingrui Guo, Zi Hui Tan, Sanghoon Lee, Li Chai, Akihiko Numata, Touati Benoukraf, Melissa Jane Fullwood, Motomi Osato, Bing Ren and Daniel G. Tenen ()
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Qiling Zhou: Cancer Science Institute of Singapore, National University of Singapore
Miao Yu: School of Life Sciences, Fudan University
Roberto Tirado-Magallanes: Cancer Science Institute of Singapore, National University of Singapore
Bin Li: Ludwig Institute for Cancer Research
Lingshi Kong: Cancer Science Institute of Singapore, National University of Singapore
Mingrui Guo: Cancer Science Institute of Singapore, National University of Singapore
Zi Hui Tan: Cancer Science Institute of Singapore, National University of Singapore
Sanghoon Lee: Cancer Science Institute of Singapore, National University of Singapore
Li Chai: Brigham and Women’s Hospital
Akihiko Numata: Cancer Science Institute of Singapore, National University of Singapore
Touati Benoukraf: Cancer Science Institute of Singapore, National University of Singapore
Melissa Jane Fullwood: Cancer Science Institute of Singapore, National University of Singapore
Motomi Osato: Cancer Science Institute of Singapore, National University of Singapore
Bing Ren: Ludwig Institute for Cancer Research
Daniel G. Tenen: Cancer Science Institute of Singapore, National University of Singapore

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: Abstract CCCTC binding factor (CTCF) is an important factor in the maintenance of chromatin–chromatin interactions, yet the mechanism regulating its binding to chromatin is unknown. We demonstrate that zinc finger protein 143 (ZNF143) is a key regulator for CTCF-bound promoter–enhancer loops. In the murine genome, a large percentage of CTCF and ZNF143 DNA binding motifs are distributed 37 bp apart in the convergent orientation. Furthermore, deletion of ZNF143 leads to loss of CTCF binding on promoter and enhancer regions associated with gene expression changes. CTCF-bound promoter–enhancer loops are also disrupted after excision of ZNF143. ZNF143-CTCF-bound promoter–enhancer loops regulate gene expression patterns essential for maintenance of murine hematopoietic stem and progenitor cell integrity. Our data suggest a common feature of gene regulation is that ZNF143 is a critical factor for CTCF-bound promoter–enhancer loops.

Date: 2021
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DOI: 10.1038/s41467-020-20282-1

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