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| Status |
Public on Aug 31, 2023 |
| Title |
BRWD1 orchestrates chromatin topology by converting static to dynamic cohesin complexes (Hi-C) |
| Organism |
Mus musculus |
| Experiment type |
Other
|
| Summary |
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. Herein, we demonstrate that in small pre-B cells, the lineage and stage-specific epigenetic reader BRWD1 reorders three-dimensional chromatin topology to affect transition between proliferative and gene recombination molecular programs. BRWD1 regulated the switch between poised and active enhancers interacting with promoters and coordinated this with Igk locus contraction. BRWD1 did so by converting chromatin-bound static cohesin to dynamic complexes competent to mediate long-range looping. Remarkably, ATP depletion recapitulated cohesin distributions observed in Brwd1-/- cells. Therefore, in small pre-B cells, cohesin conversion appears to be the main energetic mechanism dictating where dynamic looping occurs in the genome. Our findings provide a new mechanism of cohesin regulation and reveal how cohesin function can be regulated by lineage contextual mechanisms to facilitate specific cell fate transitions.
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| Overall design |
Hi-C of small pre-B cells with WT, BRWD1KO genotypes; or Immature B cells in WT genotype from mice. Two biological replicates collected.
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| Contributor(s) |
Mandal M, Maienschein-Cline M, Hu Y, Mohsin A, Veselits ML, Wright NE, Okoreeh MK, Yoon YM, Veselits J, Georgopoulos K, Clark MR |
| Citation(s) |
37985858 |
| |
| Submission date |
Dec 21, 2022 |
| Last update date |
Nov 30, 2023 |
| Contact name |
Mark Maienschein-Cline |
| E-mail(s) |
mmaiensc@uic.edu
|
| Organization name |
University of Illinois at Chicago
|
| Department |
Research Resources Center
|
| Lab |
Center for Research Informatics
|
| Street address |
1819 W Polk Ave, Rm 336 M/C 789
|
| City |
Chicago |
| State/province |
IL |
| ZIP/Postal code |
60612 |
| Country |
USA |
| |
|
| Platforms (2) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
|
| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE221519 |
BRWD1 orchestrates chromatin topology by converting static to dynamic cohesin complexes |
|
| Relations |
| BioProject |
PRJNA914725 |
| SRA |
SRP414315 |
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