Genomics

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Essential role of the Pax5 C-terminal domain in controlling B cell commitment and development


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.

ORGANISM(S): Mus musculus

PROVIDER: GSE224793 | GEO | 2023/08/24

REPOSITORIES: GEO

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