Cohesin-mediated chromatin remodeling controls the differentiation and function of conventional dendritic cells

Adams, N. M.; Galitsyna, A.; Tiniakou, I.; Esteva, E.; Lau, C. M.; Reyes, J.; Abdennur, N.; Shkolikov, A.; Yap, G. S.; Khodadadi-Jamayran, A.; Mirny, L.; Reizis, B.

doi:10.1101/2024.09.18.613709

bioRxiv · 10.1101/2024.09.18.613709

Cohesin-mediated chromatin remodeling controls the differentiation and function of conventional dendritic cells

Adams, N. M.·Galitsyna, A.·Tiniakou, I.·Esteva, E.·Lau, C. M.·Reyes, J.·Abdennur, N.·Shkolikov, A.·Yap, G. S.·Khodadadi-Jamayran, A.·Mirny, L.·Reizis, B.

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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) in vivo. 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 Irf8 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 Il12b gene reduced IL-12 production by cDC1s. Our data reveal an essential role of cohesin-mediated chromatin regulation in cell differentiation and function in vivo, and its bi-directional crosstalk with lineage-specifying transcription factors.

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Adams, N. M., Galitsyna, A., Tiniakou, I., Esteva, E., Lau, C. M., Reyes, J., Abdennur, N., Shkolikov, A., Yap, G. S., Khodadadi-Jamayran, A., Mirny, L., Reizis, B.. 2024-09-22. Cohesin-mediated chromatin remodeling controls the differentiation and function of conventional dendritic cells. https://doi.org/10.1101/2024.09.18.613709

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