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Essential role of the Pax5 C-terminal domain in controlling B cell commitment and development
- Source :
- The Journal of Experimental Medicine; December 2023, Vol. 220 Issue: 12 pe20230260-e20230260, 1p
- Publication Year :
- 2023
-
Abstract
- The B cell regulator Pax5 consists of multiple domains whose function we analyzed in vivo by deletion in Pax5. While B lymphopoiesis was minimally affected in mice with homozygous deletion of the octapeptide or partial homeodomain, both sequences were required for optimal B cell development. Deletion of the C-terminal regulatory domain 1 (CRD1) interfered with B cell development, while elimination of CRD2 modestly affected B-lymphopoiesis. Deletion of CRD1 and CRD2 arrested B cell development at an uncommitted pro-B cell stage. Most Pax5-regulated genes required CRD1 or both CRD1 and CRD2 for their activation or repression as these domains induced or eliminated open chromatin at Pax5-activated or Pax5-repressed genes, respectively. Co-immunoprecipitation experiments demonstrated that the activating function of CRD1 is mediated through interaction with the chromatin-remodeling BAF, H3K4-methylating Set1A-COMPASS, and H4K16-acetylating NSL complexes, while its repressing function depends on recruitment of the Sin3-HDAC and MiDAC complexes. These data provide novel molecular insight into how different Pax5 domains regulate gene expression to promote B cell commitment and development.
Details
- Language :
- English
- ISSN :
- 00221007 and 15409538
- Volume :
- 220
- Issue :
- 12
- Database :
- Supplemental Index
- Journal :
- The Journal of Experimental Medicine
- Publication Type :
- Periodical
- Accession number :
- ejs63991214
- Full Text :
- https://doi.org/10.1084/jem.20230260