Essential role of the Pax5 C-terminal domain in controlling B cell commitment and development.
| Autor: | Gruenbacher S; Research Institute of Molecular Pathology, Vienna BioCenter , Vienna, Austria.; Vienna BioCenter PhD Program, Doctoral School of the University of Vienna and Medical University of Vienna , Vienna, Austria., Jaritz M; Research Institute of Molecular Pathology, Vienna BioCenter , Vienna, Austria., Hill L; Research Institute of Molecular Pathology, Vienna BioCenter , Vienna, Austria., Schäfer M; Research Institute of Molecular Pathology, Vienna BioCenter , Vienna, Austria., Busslinger M; Research Institute of Molecular Pathology, Vienna BioCenter , Vienna, Austria. |
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| Jazyk: | angličtina |
| Zdroj: | The Journal of experimental medicine [J Exp Med] 2023 Dec 04; Vol. 220 (12). Date of Electronic Publication: 2023 Sep 19. |
| DOI: | 10.1084/jem.20230260 |
| Abstrakt: | 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. (© 2023 Grünbacher et al.) |
| Databáze: | MEDLINE |
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