Putative Looping Factor ZNF143/ZFP143 is an Essential Transcriptional Regulator with No Looping Function

Interactions between distal loci, including those involving enhancers and promoters, are 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 regulator of chromatin interactions, functioning either with or without CTCF. However, ZNF143/ZFP143s role in this process and its function, either with or without CTCF, are not well understood. Here, we tagged both CTCF and ZNF143/ZFP143 with dual-purpose degron/imaging tags to combinatorially assess their looping function and effect on each other. We find that ZNF143/ZFP143 possesses no general looping function in mouse and human cells, and that it largely functions independently of 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.