Cohesin: behind dynamic genome topology and gene expression reprogramming

• Published in: Trends in cell biology Vol. 31; no. 9; pp. 760 - 773
• Main Authors: Perea-Resa, Carlos, Wattendorf, Lauren, Marzouk, Sammer, Blower, Michael D.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.09.2021; Elsevier BV
• Subjects: CdLS; Cell cycle; Cell Cycle Proteins - genetics; cell identity; Chromatids; Chromatin; Chromatin - genetics; Chromosomal Proteins, Non-Histone - genetics; Cohesin; Cohesins; Cohesion; DNA loops; Extrusion; Gene Expression; Gene regulation; Genomes; Heterogeneity; Humans; Sister chromatids; Tethering; Topology; Transcription; DNA loops; cohesin; cell identity; transcription; cell cycle; CdLS
• ISSN: 0962-8924; 1879-3088
• DOI: 10.1016/j.tcb.2021.03.005

Beyond its originally discovered role tethering replicated sister chromatids, cohesin has emerged as a master regulator of gene expression. Recent advances in chromatin topology resolution and single-cell studies have revealed that cohesin has a pivotal role regulating highly dynamic chromatin interactions linked to transcription control. The dynamic association of cohesin with chromatin and its capacity to perform loop extrusion contribute to the heterogeneity of chromatin contacts. Additionally, different cohesin subcomplexes, with specific properties and regulation, control gene expression across the cell cycle and during developmental cell commitment. Here, we discuss the most recent literature in the field to highlight the role of cohesin in gene expression regulation during transcriptional shifts and its relationship with human diseases. Analysis of chromatin contacts in single cells and at nucleosome resolution evidence a highly dynamic genome topology.Cohesin is key for genome dynamism because of its capacity to extrude DNA, its dynamic chromatin loading and removal, and the existence of distinct subcomplexes with differential properties and regulation.Stromal antigen 1 and 2 (STAG1 and STAG2)-containing complexes connect cohesin functions in chromosome organization and gene expression regulation in the frame of cell differentiation.Massive cohesin removal and loading as cells transition through mitosis influence gene expression reprogramming across the cell cycle.Cohesin recycling during the telophase/G1 transition might participate in transcription restart and contribute to cell fate determination during development.