A Recurrent Network Involving the Transcription Factors PU.1 and Gfi1 Orchestrates Innate and Adaptive Immune Cell Fates

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2009 Oct 13

PMID 19818654

Citations 98

Authors

Chauncey J Spooner

Jason X Cheng

Elisabet Pujadas

Peter Laslo

Harinder Singh

Affiliations

Soon will be listed here.

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.

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