title: The chromatin remodeler Brg1 activates enhancer repertoires to establish B cell identity and modulate cell growth.
abstract: Early B cell development is orchestrated by the combined activities of the transcriptional regulators E2A, EBF1, Foxo1 and Ikaros. However, how the genome-wide binding patterns of these regulators are modulated during B lineage development remains to be determined. Here we found that in lymphoid progenitor cells, the chromatin remodeler Brg1 specified the B cell fate. In committed pro-B cells, Brg1 regulated contraction of the locus encoding the immunoglobulin heavy chain (Igh) and controlled expression of the gene encoding the transcription factor c-Myc (Myc) to modulate the expression of genes encoding products that regulate ribosome biogenesis. In committed pro-B cells, Brg1 suppressed a pre-B lineage-specific pattern of gene expression. Finally, we found that Brg1 acted mechanistically to establish B cell fate and modulate cell growth by facilitating access of lineage-specific transcription factors to enhancer repertoires.
authors.affiliation: Department of Molecular Biology, University of California, San Diego, La Jolla, California, USA.
authors.forename: Claudia
authors.initials: C
authors.lastname: Bossen
authors.affiliation: Department of Molecular Biology, University of California, San Diego, La Jolla, California, USA.
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Murre
authors.affiliation: Center for Computational Biology, Institute for Genomic Medicine, University of California, San Diego, La Jolla, California, USA.
authors.forename: Aaron N
authors.initials: AN
authors.lastname: Chang
authors.affiliation: 1] Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden. [2] Hematology Center, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Robert
authors.initials: R
authors.lastname: Mansson
authors.affiliation: Division of Cellular Immunology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Hans-Reimer
authors.initials: HR
authors.lastname: Rodewald
authors.affiliation: Department of Molecular Biology, University of California, San Diego, La Jolla, California, USA.
authors.forename: Cornelis
authors.initials: C
authors.lastname: Murre
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D042002:Chromatin Assembly and Disassembly / Q000235:genetics / Q000276:immunology; D004265:DNA Helicases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000235:genetics / Q000276:immunology*; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D017404:In Situ Hybridization, Fluorescence; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D054448:Precursor Cells, B-Lymphoid / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D034622:RNA Interference / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D007143:Immunoglobulin Heavy Chains; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; D014157:Transcription Factors; C513194:Smarca4 protein, mouse; D004265:DNA Helicases