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.
MeSH terms
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Animals
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B-Lymphocytes / immunology*
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B-Lymphocytes / metabolism
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Cell Lineage / genetics
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Cell Lineage / immunology
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Cell Proliferation*
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Cells, Cultured
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Chromatin Assembly and Disassembly / genetics
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Chromatin Assembly and Disassembly / immunology
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DNA Helicases / genetics
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DNA Helicases / immunology*
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DNA Helicases / metabolism
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Enhancer Elements, Genetic / genetics
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Enhancer Elements, Genetic / immunology*
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Flow Cytometry
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Gene Expression Regulation / genetics
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Gene Expression Regulation / immunology
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Immunoglobulin Heavy Chains / genetics
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Immunoglobulin Heavy Chains / immunology
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Immunoglobulin Heavy Chains / metabolism
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In Situ Hybridization, Fluorescence
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Mice, Knockout
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Mice, Transgenic
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Nuclear Proteins / genetics
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Nuclear Proteins / immunology*
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Nuclear Proteins / metabolism
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Precursor Cells, B-Lymphoid / immunology
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Precursor Cells, B-Lymphoid / metabolism
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Protein Binding / immunology
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Proto-Oncogene Proteins c-myc / genetics
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Proto-Oncogene Proteins c-myc / immunology
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Proto-Oncogene Proteins c-myc / metabolism
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RNA Interference / immunology
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Reverse Transcriptase Polymerase Chain Reaction
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Transcription Factors / genetics
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Transcription Factors / immunology*
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Transcription Factors / metabolism
Substances
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Immunoglobulin Heavy Chains
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Nuclear Proteins
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Proto-Oncogene Proteins c-myc
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Transcription Factors
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Smarca4 protein, mouse
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DNA Helicases