title: Stage-specific control of early B cell development by the transcription factor Ikaros.
abstract: The transcription factor Ikaros is an essential regulator of lymphopoiesis. Here we studied its B cell-specific function by conditional inactivation of the gene encoding Ikaros (Ikzf1) in pro-B cells. B cell development was arrested at an aberrant 'pro-B cell' stage characterized by increased cell adhesion and loss of signaling via the pre-B cell signaling complex (pre-BCR). Ikaros activated genes encoding signal transducers of the pre-BCR and repressed genes involved in the downregulation of pre-BCR signaling and upregulation of the integrin signaling pathway. Unexpectedly, derepression of expression of the transcription factor Aiolos did not compensate for the loss of Ikaros in pro-B cells. Ikaros induced or suppressed active chromatin at regulatory elements of activated or repressed target genes. Notably, binding of Ikaros and expression of its target genes were dynamically regulated at distinct stages of early B lymphopoiesis.
authors: 1] Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria. [2].
authors: Tanja A
authors: TA
authors: Schwickert
authors: 1] Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria. [2].
authors: Hiromi
authors: H
authors: Tagoh
authors: Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria.
authors: Sinan
authors: S
authors: Gültekin
authors: 1] Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria. [2].
authors: Aleksandar
authors: A
authors: Dakic
authors: Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria.
authors: Elin
authors: E
authors: Axelsson
authors: Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria.
authors: Martina
authors: M
authors: Minnich
authors: Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria.
authors: Anja
authors: A
authors: Ebert
authors: Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria.
authors: Barbara
authors: B
authors: Werner
authors: Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria.
authors: Mareike
authors: M
authors: Roth
authors: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
authors: Luisa
authors: L
authors: Cimmino
authors: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
authors: Ross A
authors: RA
authors: Dickins
authors: Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria.
authors: Johannes
authors: J
authors: Zuber
authors: Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria.
authors: Markus
authors: M
authors: Jaritz
authors: Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria.
authors: Meinrad
authors: M
authors: Busslinger
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D047369:Chromatin Immunoprecipitation; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology; D055785:Gene Knockdown Techniques; D051740:Ikaros Transcription Factor / Q000276:immunology* / Q000378:metabolism; D038041:Lymphopoiesis / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology* / Q000276:immunology / Q000378:metabolism
chemical_list: C497238:Zfpn1a1 protein, mouse; D051740:Ikaros Transcription Factor