CTCF N-terminal Domain Regulates Clustered Protocadherin Gene Expression by Enhancing Cohesin Processivity

Abstract

AbstractCTCF architects 3D genome folding by anchoring or forestalling cohesin loop extrusion, but the exact mechanism remains obscure. Here, using clustered protocadherins (cPcdh) as model genes, we report that CTCF stabilizes or facilitates cohesin loop extrusion by enhancing its processivity. Specifically, we show that, compared with thePcdh αandγclusters, thePcdhβcluster is greatly affected upon CTCFY226A/F228Amutation in the N-terminal domain. Given the long-range distance of thePcdhβcluster from the distal enhancer, this finding has interesting implications in CTCF regulation of cohesin processivity along the linear chromatin during DNA loop extrusion. In particular, the effect on cohesin processivity upon CTCFY226A/F228Amutation is conspicuously similar to that of WAPL overexpression, demonstrating that, contrary to the general view of blocking or forestalling cohesin, CTCF actually enhances or facilitates cohesin loop extrusion.