Roles of cohesin in chromosome architecture and gene expression

Abstract

Cohesin-mediated chromatin organization plays an important role in formation and stabilization of chromosome architecture and gene regulation. Mechanisms by which cohesin shapes chromosome and regulates gene expression remain unclear. The present article overviews biological characters and functions of cohesin and core subunits and explores roles of regulatory factors (e.g. Pds5, Wapl, and Eco1) in dynamic behaviors of cohesin. Cohesin interacts with CCCTC binding factor (CTCF) and other factors to maintain and stabilize multi-dimensional organizations of topological loops and distances between sites during cell segmentation. We also describe functional roles of cohesin in cell cycle by entrapping sister chromatids to form embrace and handcuff models, loading onto chromatin, establishing cohesion function, and regulating removal of cohesin and associated factors from the chromosome arm through prophase pathway or at onset of anaphase. It is questioned whether those factors associated with cohesin-regulated processes can be identified as biology- or disease-specific biomarkers and druggable targets to dynamically monitor changes during phasing, staging, progressing, and responding of diseases. It is also expected to explore heterogenetic roles of cohesin between single cells and regulatory roles of cohesin in trans-omic profiles and functions. Further understanding of cohesin functions will be beneficial to improve diagnosis and treatment of cohesinopathies.

Keywords: 3D genome; Cohesin; Cohesinopathy; Cohesion.