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PLoS One. 2016 Jul 28;11(7):e0160344. doi: 10.1371/journal.pone.0160344. eCollection 2016.

Threshold Levels of Gfi1 Maintain E2A Activity for B Cell Commitment via Repression of Id1.

Author information

1
Institut de recherches cliniques de Montréal (IRCM), Montréal, Québec, Canada.
2
Département de microbiologie, infectiologie et immunologie, Université de Montréal, Montréal, Québec, Canada.
3
Division of Experimental Medicine, McGill University, Montreal, Canada.
4
Département de médecine, Université de Montréal, Montréal, Québec, Canada.
5
Department of Hematology, University Hospital, Essen, Germany.

Abstract

A regulatory circuit that controls myeloid versus B lymphoid cell fate in hematopoietic progenitors has been proposed, in which a network of the transcription factors Egr1/2, Nab, Gfi1 and PU.1 forms the core element. Here we show that a direct link between Gfi1, the transcription factor E2A and its inhibitor Id1 is a critical element of this regulatory circuit. Our data suggest that a certain threshold of Gfi1 is required to gauge E2A activity by adjusting levels of Id1 in multipotent progenitors, which are the first bipotential myeloid/lymphoid-restricted progeny of hematopoietic stem cells. If Gfi1 levels are high, Id1 is repressed enabling E2A to activate a specific set of B lineage genes by binding to regulatory elements for example the IL7 receptor gene. If Gfi1 levels fall below a threshold, Id1 expression increases and renders E2A unable to function, which prevents hematopoietic progenitors from engaging along the B lymphoid lineage.

PMID:
27467586
PMCID:
PMC4965025
DOI:
10.1371/journal.pone.0160344
[Indexed for MEDLINE]
Free PMC Article

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