Format

Send to

Choose Destination
Immunity. 2009 Oct 16;31(4):576-86. doi: 10.1016/j.immuni.2009.07.011. Epub 2009 Oct 8.

A recurrent network involving the transcription factors PU.1 and Gfi1 orchestrates innate and adaptive immune cell fates.

Author information

1
Howard Hughes Medical Institute, The University of Chicago, GCIS W522, Chicago, IL 60637, USA.

Abstract

The transcription factor PU.1, encoded by the Sfpi1 gene, functions in a graded manner to regulate macrophage versus B cell generation; its higher concentration favors the macrophage fate. We demonstrated that Gfi1 reciprocally promoted B cell fate choice at the expense of myeloid progeny. Gfi1(-/-) multipotential progenitors (MPPs) were unable to constrain the expression of PU.1 because Gfi1 functioned to repress the Sfpi1 gene by displacing PU.1 from positive autoregulatory elements. Attenuating a transcriptional module composed of PU.1 and Egr suppressed the B lineage developmental defects of Gfi1(-/-) MPPs. Finally Ikaros, a transcription factor required for B cell development, promoted Gfi1 and antagonized PU.1 expression in MPPs. Our results reveal that a core transcriptional regulatory network used for directing cell fate choice in the innate immune system has been co-opted by Ikaros to orchestrate B lymphocyte generation. These findings have important implications for the evolution of the adaptive immune system.

PMID:
19818654
PMCID:
PMC4373467
DOI:
10.1016/j.immuni.2009.07.011
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center