title: The ARID family transcription factor bright is required for both hematopoietic stem cell and B lineage development.
abstract: Bright/Arid3a has been characterized both as an activator of immunoglobulin heavy-chain transcription and as a proto-oncogene. Although Bright expression is highly B lineage stage restricted in adult mice, its expression in the earliest identifiable hematopoietic stem cell (HSC) population suggests that Bright might have additional functions. We showed that >99% of Bright(-/-) embryos die at midgestation from failed hematopoiesis. Bright(-/-) embryonic day 12.5 (E12.5) fetal livers showed an increase in the expression of immature markers. Colony-forming assays indicated that the hematopoietic potential of Bright(-/-) mice is markedly reduced. Rare survivors of lethality, which were not compensated by the closely related paralogue Bright-derived protein (Bdp)/Arid3b, suffered HSC deficits in their bone marrow as well as B lineage-intrinsic developmental and functional deficiencies in their peripheries. These include a reduction in a natural antibody, B-1 responses to phosphocholine, and selective T-dependent impairment of IgG1 class switching. Our results place Bright/Arid3a on a select list of transcriptional regulators required to program both HSC and lineage-specific differentiation.
authors.affiliation: Immunobiology and Cancer Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73126, USA.
authors.forename: Carol F
authors.initials: CF
authors.lastname: Webb
authors.forename: James
authors.initials: J
authors.lastname: Bryant
authors.forename: Melissa
authors.initials: M
authors.lastname: Popowski
authors.forename: Laura
authors.initials: L
authors.lastname: Allred
authors.forename: Dongkoon
authors.initials: D
authors.lastname: Kim
authors.forename: June
authors.initials: J
authors.lastname: Harriss
authors.forename: Christian
authors.initials: C
authors.lastname: Schmidt
authors.forename: Cathrine A
authors.initials: CA
authors.lastname: Miner
authors.forename: Kira
authors.initials: K
authors.lastname: Rose
authors.forename: Hwei-Ling
authors.initials: HL
authors.lastname: Cheng
authors.forename: Courtney
authors.initials: C
authors.lastname: Griffin
authors.forename: Philip W
authors.initials: PW
authors.lastname: Tucker
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D019070:Cell Lineage; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005804:Genes, Lethal; D006410:Hematopoiesis / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D017578:Immunoglobulin Class Switching / Q000235:genetics; D038041:Lymphopoiesis / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010767:Phosphorylcholine / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000906:Antibodies; C097532:Arid3a protein, mouse; D004268:DNA-Binding Proteins; D014157:Transcription Factors; D010767:Phosphorylcholine