ZNF143 deletion alters enhancer/promoter looping and CTCF/cohesin geometry

Mo Zhang; Haiyan Huang; Jingwei Li; Qiang Wu

doi:10.1016/j.celrep.2023.113663

ZNF143 deletion alters enhancer/promoter looping and CTCF/cohesin geometry

Cell Rep. 2024 Jan 23;43(1):113663. doi: 10.1016/j.celrep.2023.113663. Epub 2024 Jan 10.

Authors

Mo Zhang¹, Haiyan Huang¹, Jingwei Li¹, Qiang Wu²

Affiliations

¹ Center for Comparative Biomedicine, Ministry of Education Key Laboratory of Systems Biomedicine, State Key Laboratory of Medical Genomics, Institute of Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China; WLA Laboratories, Shanghai 201203, China.
² Center for Comparative Biomedicine, Ministry of Education Key Laboratory of Systems Biomedicine, State Key Laboratory of Medical Genomics, Institute of Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China; WLA Laboratories, Shanghai 201203, China. Electronic address: qiangwu@sjtu.edu.cn.

PMID: 38206813
DOI: 10.1016/j.celrep.2023.113663

Abstract

The transcription factor ZNF143 contains a central domain of seven zinc fingers in a tandem array and is involved in 3D genome construction. However, the mechanism by which ZNF143 functions in chromatin looping remains unclear. Here, we show that ZNF143 directionally recognizes a diverse range of genomic sites directly within enhancers and promoters and is required for chromatin looping between these sites. In addition, ZNF143 is located between CTCF and cohesin at numerous CTCF sites, and ZNF143 removal narrows the space between CTCF and cohesin. Moreover, genetic deletion of ZNF143, in conjunction with acute CTCF degradation, reveals that ZNF143 and CTCF collaborate to regulate higher-order topological chromatin organization. Finally, CTCF depletion enlarges direct ZNF143 chromatin looping. Thus, ZNF143 is recruited by CTCF to the CTCF sites to regulate CTCF/cohesin configuration and TAD (topologically associating domain) formation, whereas directional recognition of genomic DNA motifs directly by ZNF143 itself regulates promoter activity via chromatin looping.

Keywords: CP: Molecular biology; CTCF; TAD; ZNF143; chromatin loop; cohesin; compartment; enhancer; promoter; topological insulator; transcription.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Binding Sites
CCCTC-Binding Factor / metabolism
Cell Cycle Proteins / genetics
Cell Cycle Proteins / metabolism
Chromatin
Chromosomal Proteins, Non-Histone* / metabolism
Cohesins*

Substances

Cohesins
Chromosomal Proteins, Non-Histone
CCCTC-Binding Factor
Chromatin
Cell Cycle Proteins