ZNF143 deletion alters enhancer/promoter looping and CTCF/cohesin geometry [HiChIP]
The transcription factor ZNF143 contains seven tandem zinc fingers 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 diverse genomic sites 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 depletion, revealed that ZNF143 and CTCF collaborate to regulate higher-order genome organization. Thus, ZNF143 is recruited by CTCF to the CTCF sites to regulate TAD formation and genome compartmentalization whereas directional recognition of DNA motifs directly by ZNF143 itself regulates promoter activity via chromatin looping. Overall design: HiChIP for ZNF143, CTCF, and RAD21 in wild type HEC-1-B cells, ZNF143KO cells, or in CTCF-AID cell that treated with auxin for 0h or 24h.