Open AccessThreshold Levels of Gfi1 Maintain E2A Activity for B Cell Commitment via Repression of Id1
Author(s) -
Jennifer Fraszczak,
Anne Helness,
Riyan Chen,
Charles Vadnais,
François Robert,
Cyrus Khandanpour,
Tarik Möröy
Publication year - 2016
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0160344
Subject(s) - myeloid , haematopoiesis , transcription factor , biology , progenitor cell , psychological repression , lymphopoiesis , b cell , microbiology and biotechnology , cancer research , gene knockdown , stem cell , gene , genetics , gene expression , antibody
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.