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Nat Commun. 2016 Aug 10;7:12376. doi: 10.1038/ncomms12376.

MEF2C protects bone marrow B-lymphoid progenitors during stress haematopoiesis.

Author information

1
Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, California 90095, USA.
2
Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, California 90095, USA.
3
Molecular Biology Institute, UCLA, Los Angeles, California 90095, USA.
4
Institute of Molecular and Cell Biology, University of Tartu, Tartu 51010, Estonia.
5
Department of Molecular Toxicology, UCLA, Los Angeles, California 90095, USA.
6
Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California 90095, USA.
7
Department of Biological Chemistry, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA.
8
The Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California San Francisco, San Francisco, California 94143, USA.

Abstract

DNA double strand break (DSB) repair is critical for generation of B-cell receptors, which are pre-requisite for B-cell progenitor survival. However, the transcription factors that promote DSB repair in B cells are not known. Here we show that MEF2C enhances the expression of DNA repair and recombination factors in B-cell progenitors, promoting DSB repair, V(D)J recombination and cell survival. Although Mef2c-deficient mice maintain relatively intact peripheral B-lymphoid cellularity during homeostasis, they exhibit poor B-lymphoid recovery after sub-lethal irradiation and 5-fluorouracil injection. MEF2C binds active regulatory regions with high-chromatin accessibility in DNA repair and V(D)J genes in both mouse B-cell progenitors and human B lymphoblasts. Loss of Mef2c in pre-B cells reduces chromatin accessibility in multiple regulatory regions of the MEF2C-activated genes. MEF2C therefore protects B lymphopoiesis during stress by ensuring proper expression of genes that encode DNA repair and B-cell factors.

PMID:
27507714
PMCID:
PMC4987520
DOI:
10.1038/ncomms12376
[Indexed for MEDLINE]
Free PMC Article

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