title: Threshold Levels of Gfi1 Maintain E2A Activity for B Cell Commitment via Repression of Id1.
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.
authors.affiliation: Institut de recherches cliniques de Montréal (IRCM), Montréal, Québec, Canada.|Département de microbiologie, infectiologie et immunologie, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Fraszczak
authors.affiliation: Institut de recherches cliniques de Montréal (IRCM), Montréal, Québec, Canada.|Division of Experimental Medicine, McGill University, Montreal, Canada.
authors.forename: Anne
authors.initials: A
authors.lastname: Helness
authors.affiliation: Institut de recherches cliniques de Montréal (IRCM), Montréal, Québec, Canada.
authors.forename: Riyan
authors.initials: R
authors.lastname: Chen
authors.affiliation: Institut de recherches cliniques de Montréal (IRCM), Montréal, Québec, Canada.|Département de microbiologie, infectiologie et immunologie, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Charles
authors.initials: C
authors.lastname: Vadnais
authors.affiliation: Institut de recherches cliniques de Montréal (IRCM), Montréal, Québec, Canada.|Département de médecine, Université de Montréal, Montréal, Québec, Canada.
authors.forename: François
authors.initials: F
authors.lastname: Robert
authors.affiliation: Department of Hematology, University Hospital, Essen, Germany.
authors.forename: Cyrus
authors.initials: C
authors.lastname: Khandanpour
authors.affiliation: Institut de recherches cliniques de Montréal (IRCM), Montréal, Québec, Canada.|Département de microbiologie, infectiologie et immunologie, Université de Montréal, Montréal, Québec, Canada.|Division of Experimental Medicine, McGill University, Montreal, Canada.
authors.forename: Tarik
authors.initials: T
authors.lastname: Möröy
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D020869:Gene Expression Profiling; D051798:Inhibitor of Differentiation Protein 1 / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D051798:Inhibitor of Differentiation Protein 1; D014157:Transcription Factors; C079873:Gfi1 protein, mouse; C497455:Idb1 protein, mouse; C075668:Tcf3 protein, mouse