Work

CCCTC-binding factor N-terminal domain regulates clustered protocadherin gene expression by enhancing cohesin processivity

Year: 2025

Type: article

Abstract: CTCF (CCCTC-binding factor) instructs three-dimensional (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 assists or facilitates cohesin loop extrusion by enhancing its processivity. Specifically, we show that, compared with the Pcdh α and γ gene clusters, the Pcdhβ cluster is greatly affected upon CTCF Y226A/F228A mutation in the N-terminal domain. Given the long-range distance of the Pcdhβ cluster 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 CTCF Y226A/F228A mutation is conspicuously similar to that of WAPL overexpression, suggesting that, in addition to the general view of blocking or forestalling cohesin, CTCF may actually enhance or facilitate cohesin loop extrusion during 3D genome folding. We conclude that CTCF enhances cohesin enrichments via the N-terminal YDF motif in clustered protocadherin genes in a genomic-distance biased manner.

Source: Journal of Biological Chemistry

DOI: 10.1016/j.jbc.2025.108337

Authors: Yijun Zhang, Qiang Wu

Institutions: Shanghai Jiao Tong University, State Key Laboratory of Medical Genomics

Language: English

Topic: Genomics and Chromatin Dynamics

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $3,430

Funders: National Natural Science Foundation of China, National Key Research and Development Program of China