Putative looping factor ZNF143/ZFP143 is an essential transcriptional regulator with no looping function [ChIP-seq]

Interactions between distal loci in mammalian genomes, including those involving enhancers and promoters, are thought to be a central mechanism of gene regulation in mammals, yet the protein regulators of these interactions remain largely undetermined. The zinc finger transcription factor ZNF143/ZFP143 has been strongly implicated as a factor that regulates chromatin interactions, functioning either with or without CTCF. However, ZNF143/ZFP143’s role in this process and its function with or without CTCF are not well understood. Here, we tagged both CTCF and ZNF143/ZFP143 with dual-purpose degron/imaging tags to combinatorically assess their loop function and effect on each other. We find that ZNF143/ZFP143 possesses no general looping function, and that it largely functions independently to CTCF. Instead, ZNF143/ZFP143 is an essential and highly conserved transcription factor possessing an extremely stable chromatin residence time (>20 min) that regulates an important subset of mitochondrial and ribosomal genes. We generated two replicates of Micro-C, ZFP143 ChIP-seq, CTCF ChIP-seq, and PRO-seq per cell line and condition in two mouse embryonic stem cell (mESC) cell lines with the following conditions: untreated, three-hour ZFP143 depletion by 5-Ph-IAA/HaloPROTAC3 treatment, three-hour CTCF depletion by dTag-13 treatment, or three-hour depletion of both ZFP143 and CTCF. We also generated two replicates of Micro-C, ZFP143 ChIP-seq, CTCF ChIP-seq, and PRO-seq per condition in an additional mESC cell line with untreated and three-hour ZFP143 depletion by dTag-13 conditions. Additionally, we performed two replicates of Micro-C per condition in a HEK293T cell line with untreated and three-hour ZNF143 depletion by IAA conditions.