Author Information
1Cancer Science Institute of Singapore, National University of Singapore, 117599, Singapore, Singapore.
2YLL School of Medicine, National University of Singapore, 119228, Singapore, Singapore.
3School of Life Sciences, Fudan University, Shanghai, China.
4Ludwig Institute for Cancer Research, La Jolla, CA, 92093, USA.
5Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
6Department of Pathology, Brigham and Women’s Hospital, Boston, MA, 02115, USA.
7Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, Fukuoka, Japan.
8Division of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL, A1B 3V6, Canada.
9School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, 637551, Singapore, Singapore.
10Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, Proteos, 138673, Singapore.
11Department of Cellular & Molecular Medicine, Moores Cancer Center and Institute of Genome Medicine, UCSD School of Medicine, 9500 Gilman Drive, La Jolla, CA, 92093, USA.
12Cancer Science Institute of Singapore, National University of Singapore, 117599, Singapore, Singapore. daniel.tenen@nus.edu.sg.
13Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, 02115, USA. daniel.tenen@nus.edu.sg.
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.
PMID: 33397967 PMCID: PMC778251 DOI: 10.1038/s41467-020-20282-1