Journal Article Preprint Epublish 2 citations
PubMed: 39345451 DOI: 10.1101/2024.09.18.613709
Cohesin-mediated chromatin remodeling controls the differentiation and function of conventional dendritic cells.
bioRxiv
Authors: Nicholas M Adams, Aleksandra Galitsyna, Ioanna Tiniakou, Eduardo Esteva, Colleen M Lau, Jojo Reyes, Nezar Abdennur, Alexey Shkolikov, George S Yap, Alireza Khodadadi-Jamayran, Leonid A Mirny, Boris Reizis
Affiliations
- Department of Pathology, New York University Grossman School of Medicine, New York, NY 10016, USA.
- Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
- Applied Bioinformatics Laboratories, New York University Grossman School of Medicine, New York, NY 10016, USA.
- Department of Microbiology and Immunology, Cornell University College of Veterinary Medicine, Ithaca, NY 14853, USA.
- Center for Immunity and Inflammation, Department of Medicine, New Jersey Medical School, Rutgers University, Newark NJ 07101, USA.
- Department of Genomics and Computational Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
- Department of Systems Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
- independent researcher.
- Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Abstract
The cohesin protein complex extrudes chromatin loops, stopping at CTCF-bound sites, to organize chromosomes into topologically associated domains, yet the biological implications of this process are poorly understood. We show that cohesin is required for the post-mitotic differentiation and function of antigen-presenting dendritic cells (DCs), particularly for antigen cross-presentation and IL-12 secretion by type 1 conventional DCs (cDC1s) . The chromatin organization of DCs was shaped by cohesin and the DC-specifying transcription factor IRF8, which controlled chromatin looping and chromosome compartmentalization, respectively. Notably, optimal expression of IRF8 itself required CTCF/cohesin-binding sites demarcating the gene. During DC activation, cohesin was required for the induction of a subset of genes with distal enhancers. Accordingly, the deletion of CTCF sites flanking the gene reduced IL-12 production by cDC1s. Our data reveal an essential role of cohesin-mediated chromatin regulation in cell differentiation and function , and its bi-directional crosstalk with lineage-specifying transcription factors.
MeSH
Cells, Genes, Transcription Factors, Chromatin, Dendritic Cells, Chromosomes