Full circle: a brief history of cohesin and the regulation of gene expression

• Published in: The FEBS journal Vol. 290; no. 7; pp. 1670 - 1687
• Main Author: Horsfield, Julia A.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.04.2023
• Subjects: Animals; BRD4; Cell Cycle Proteins - metabolism; Chromatin; Chromatin - genetics; Chromosomal Proteins, Non-Histone - genetics; Chromosomal Proteins, Non-Histone - metabolism; Cohesin; Cohesins; Cohesion; CTCF; Depletion; DNA; DNA damage; DNA repair; Drosophila; Drosophila melanogaster; Extrusion; Gene expression; Gene Expression Regulation; genes; Genomes; Hi‐C; insulator; loop extrusion; Mitosis; Polycomb; replication; topologically associated domain; transcription; transcription (genetics); replication; cohesin; transcription; Hi-C; Polycomb; topologically associated domain; CTCF; insulator; BRD4; loop extrusion
• ISSN: 1742-464X; 1742-4658; 1742-4658
• DOI: 10.1111/febs.16362

The cohesin complex has a range of crucial functions in the cell. Cohesin is essential for mediating chromatid cohesion during mitosis, for repair of double‐strand DNA breaks, and for control of gene transcription. This last function has been the subject of intense research ever since the discovery of cohesin's role in the long‐range regulation of the cut gene in Drosophila. Subsequent research showed that the expression of some genes is exquisitely sensitive to cohesin depletion, while others remain relatively unperturbed. Sensitivity to cohesin depletion is also remarkably cell type‐ and/or condition‐specific. The relatively recent discovery that cohesin is integral to forming chromatin loops via loop extrusion should explain much of cohesin's gene regulatory properties, but surprisingly, loop extrusion has failed to identify a ‘one size fits all’ mechanism for how cohesin controls gene expression. This review will illustrate how early examples of cohesin‐dependent gene expression integrate with later work on cohesin's role in genome organization to explain mechanisms by which cohesin regulates gene expression. Deficiencies in the cohesin complex cause human developmental disorders and cancers, primarily owing to altered gene expression. This review integrates past and present knowledge on cohesin's gene expression role. Specific topics include cohesin's cooperation with CTCF; cohesin interaction with the transcriptional machinery; the relationships between cohesin, Polycomb group proteins, and BRD4; cohesin distribution through the genome, especially in relation to origins of DNA replication; and cohesin's role in transcription induction.