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Nat Immunol. 2015 Jul;16(7):775-84. doi: 10.1038/ni.3170. Epub 2015 May 18.

The chromatin remodeler Brg1 activates enhancer repertoires to establish B cell identity and modulate cell growth.

Author information

1
Department of Molecular Biology, University of California, San Diego, La Jolla, California, USA.
2
Center for Computational Biology, Institute for Genomic Medicine, University of California, San Diego, La Jolla, California, USA.
3
1] Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden. [2] Hematology Center, Karolinska University Hospital, Stockholm, Sweden.
4
Division of Cellular Immunology, German Cancer Research Center, Heidelberg, Germany.

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.

PMID:
25985234
PMCID:
PMC4474778
DOI:
10.1038/ni.3170
[Indexed for MEDLINE]
Free PMC Article

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