Beyond genomic weaving: molecular roles for CTCF outside cohesin loop extrusion

Abstract

CCCTC-binding factor (CTCF) is a key regulator of 3D genome organization and transcriptional activity. Beyond its well-characterized role in facilitating cohesin-mediated loop extrusion, CTCF exhibits several cohesin-independent activities relevant to chromatin structure and various nuclear processes. These functions include patterning of nucleosome arrangement and chromatin accessibility through interactions with ATP-dependent chromatin remodelers. In addition to influencing transcription, DNA replication, and DNA repair in ways that are separable from its role in loop extrusion, CTCF also interacts with RNA and contributes to RNA splicing and condensation of transcriptional activators. Here, we review recent insight into cohesin-independent activities of CTCF, highlighting its multifaceted roles in chromatin biology and transcriptional regulation.