Cohesin-Mediated Chromatin Interactions and Autoimmunity
Review article, 2022

Proper physiological functioning of any cell type requires ordered chromatin organization. In this context, cohesin complex performs important functions preventing premature separation of sister chromatids after DNA replication. In partnership with CCCTC-binding factor, it ensures insulator activity to organize enhancers and promoters within regulatory chromatin. Homozygous mutations and dysfunction of individual cohesin proteins are embryonically lethal in humans and mice, which limits in vivo research work to embryonic stem cells and progenitors. Conditional alleles of cohesin complex proteins have been generated to investigate their functional roles in greater detail at later developmental stages. Thus, genome regulation enabled by action of cohesin proteins is potentially crucial in lineage cell development, including immune homeostasis. In this review, we provide current knowledge on the role of cohesin complex in leukocyte maturation and adaptive immunity. Conditional knockout and shRNA-mediated inhibition of individual cohesin proteins in mice demonstrated their importance in haematopoiesis, adipogenesis and inflammation. Notably, these effects occur rather through changes in transcriptional gene regulation than through expected cell cycle defects. This positions cohesin at the crossroad of immune pathways including NF-kB, IL-6, and IFNγ signaling. Cohesin proteins emerged as vital regulators at early developmental stages of thymocytes and B cells and after antigen challenge. Human genome-wide association studies are remarkably concordant with these findings and present associations between cohesin and rheumatoid arthritis, multiple sclerosis and HLA-B27 related chronic inflammatory conditions. Furthermore, bioinformatic prediction based on protein-protein interactions reveal a tight connection between the cohesin complex and immune relevant processes supporting the notion that cohesin will unearth new clues in regulation of autoimmunity.

immune signaling

CCCTC-binding factor

cohesin

autoimmunity

genome organization

Author

Venkataragavan Chandrasekaran

University of Gothenburg

Nina Oparina

Sahlgrenska University Hospital

Maria-Jose Garcia-Bonete

University of Gothenburg

Caroline Wasén

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Brigham and Women's Hospital

Malin C. Erlandsson

University of Gothenburg

Eric Malmhäll Bah

University of Gothenburg

Karin M.E. Andersson

University of Gothenburg

Maja Jensen

University of Gothenburg

Sofia T. Silfverswärd

University of Gothenburg

Gergely Katona

University of Gothenburg

Maria Bokarewa

University of Gothenburg

Sahlgrenska University Hospital

Frontiers in Immunology

1664-3224 (eISSN)

Vol. 13 840002

Subject Categories

Cell Biology

Cell and Molecular Biology

Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

DOI

10.3389/fimmu.2022.840002

More information

Latest update

3/11/2022