BRWD1 orchestrates small pre-B cell chromatin topology by converting static to dynamic cohesin.

Malay Mandal, Mark Maienschein-Cline, Yeguang Hu, Azam Mohsin, Margaret L Veselits, Nathaniel E Wright, Michael K Okoreeh, Young Me Yoon, Jacob Veselits, Katia Georgopoulos, Marcus R Clark

Nature immunology 2024 Jan

filter terms:

Lymphocyte development consists of sequential and mutually exclusive cell states of proliferative selection and antigen receptor gene recombination. Transitions between each state require large, coordinated changes in epigenetic landscapes and transcriptional programs. How this occurs remains unclear. Here we demonstrate that in small pre-B cells, the lineage and stage-specific epigenetic reader bromodomain and WD repeat-containing protein 1 (BRWD1) reorders three-dimensional chromatin topology to affect the transition between proliferative and gene recombination molecular programs. BRWD1 regulated the switch between poised and active enhancers interacting with promoters, and coordinated this switch with Igk locus contraction. BRWD1 did so by converting chromatin-bound static to dynamic cohesin competent to mediate long-range looping. ATP-depletion revealed cohesin conversion to be the main energetic mechanism dictating dynamic chromatin looping. Our findings provide a new mechanism of cohesin regulation and reveal how cohesin function can be dictated by lineage contextual mechanisms to facilitate specific cell fate transitions. © 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.

Citation

Malay Mandal, Mark Maienschein-Cline, Yeguang Hu, Azam Mohsin, Margaret L Veselits, Nathaniel E Wright, Michael K Okoreeh, Young Me Yoon, Jacob Veselits, Katia Georgopoulos, Marcus R Clark. BRWD1 orchestrates small pre-B cell chromatin topology by converting static to dynamic cohesin. Nature immunology. 2024 Jan;25(1):129-141