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

ZNF143 介导小鼠造血干细胞和祖细胞功能所需的 CTCF 结合启动子增强子环

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作者: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, Daniel G Tenen

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.

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