title: Transcription factor miz-1 is required to regulate interleukin-7 receptor signaling at early commitment stages of B cell differentiation.
abstract: B cell development requires the coordinated action of transcription factors and cytokines, in particular interleukin-7 (IL-7). We report that mice lacking the POZ (Poxvirus and zinc finger) domain of the transcription factor Miz-1 (Zbtb17(ΔPOZ/ΔPOZ)) almost entirely lacked follicular B cells, as shown by the fact that their progenitors failed to activate the Jak-Stat5 pathway and to upregulate the antiapoptotic gene Bcl2 upon IL-7 stimulation. We show that Miz-1 exerted a dual role in the interleukin-7 receptor (IL-7R) pathway by directly repressing the Janus kinase (Jak) inhibitor suppressor of cytokine signaling 1 (Socs1) and by activating Bcl2 expression. Zbtb17(ΔPOZ/ΔPOZ) (Miz-1-deficient) B cell progenitors had low expression of early B cell genes as transcription factor 3 (Tcf3) and early B cell factor 1 (Ebf1) and showed a propensity for apoptosis. Only the combined re-expression of Bcl2 and Ebf1 could reconstitute the ability of Miz-1-deficient precursors to develop into CD19(+) B cells.
authors.affiliation: Institut de recherches cliniques de Montréal (IRCM), Montréal, Quebec H2W 1R7, Canada.
authors.forename: Christian
authors.initials: C
authors.lastname: Kosan
authors.forename: Ingrid
authors.initials: I
authors.lastname: Saba
authors.forename: Maren
authors.initials: M
authors.lastname: Godmann
authors.forename: Stefanie
authors.initials: S
authors.lastname: Herold
authors.forename: Barbara
authors.initials: B
authors.lastname: Herkert
authors.forename: Martin
authors.initials: M
authors.lastname: Eilers
authors.forename: Tarik
authors.initials: T
authors.lastname: Möröy
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D001853:Bone Marrow / Q000473:pathology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D050828:Protein Inhibitors of Activated STAT / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D020395:Receptors, Interleukin-7 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D044767:Ubiquitin-Protein Ligases; D051025:bcl-Associated Death Protein / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology
chemical_list: D009687:Nuclear Proteins; D050828:Protein Inhibitors of Activated STAT; D020395:Receptors, Interleukin-7; D051025:bcl-Associated Death Protein; C485521:Miz1 protein, mouse; D044767:Ubiquitin-Protein Ligases