| First Author | Gruenbacher S | Year | 2023 |
| Journal | J Exp Med | Volume | 220 |
| Issue | 12 | PubMed ID | 37725138 |
| Mgi Jnum | J:340763 | Mgi Id | MGI:7530592 |
| Doi | 10.1084/jem.20230260 | Citation | Gruenbacher S, et al. (2023) Essential role of the Pax5 C-terminal domain in controlling B cell commitment and development. J Exp Med 220(12) |
| abstractText | 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. |
