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.

journal_name

Mol Cell Biol

authors

Webb CF,Bryant J,Popowski M,Allred L,Kim D,Harriss J,Schmidt C,Miner CA,Rose K,Cheng HL,Griffin C,Tucker PW

doi

10.1128/MCB.01448-10

subject

Has Abstract

pub_date

2011-03-01 00:00:00

pages

1041-53

issue

5

eissn

0270-7306

issn

1098-5549

pii

MCB.01448-10

journal_volume

31

pub_type

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