Analyses of ZNF143 reveal single-nucleotide architectural principles of the Pcdh HS5-1 enhancer

DNA looping and TAD formations are critical for multiple basic physiological activities of cells. The ZNF143 protein contains 7 zinc fingers, and is involved in 3D genome construction. Here, we show that ZNF143 regulates the chromosome folding through two kinds of mechanisms. First, ZNF143 interacts with CTCF at CTCF binding sites (CBS) and stabilizes the interaction between CTCF and cohesin. The CTCF or cohesin depletion disrupts the binding of ZNF143 on CBS, and ZNF143 knockout narrows the space between CTCF and cohesin, and decreases the chromosome interaction. Second, ZNF143 could directly bind DNA, which is enriched at the boundaries of TADs. Removing them slightly decreases the interactions of TADs and loops, but significantly causes A/B compartment transformation, perhaps due to the changes of the gene expressions after removing ZNF143. In summary, ZNF143 is recruited by CTCF to regulate loops and TADs, while ZNF143 itself also influences TAD formations and higher-order compartment segregation. Analyses of ZNF143 reveal single-nucleotide architectural principles of the Pcdh HS5-1 enhancer