MEF2C protects bone marrow B-lymphoid progenitors during stress haematopoiesis

Wenyuan Wang, Tonis Org, Amélie Montel-Hagen, Peter D. Pioli, Dan Duan, Edo Israely, Daniel Malkin, Trent Su, Johanna Flach, Siavash K. Kurdistani, Robert H. Schiestl and Hanna K. A. Mikkola ()
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Wenyuan Wang: Cell and Developmental Biology, University of California Los Angeles
Tonis Org: Cell and Developmental Biology, University of California Los Angeles
Amélie Montel-Hagen: Cell and Developmental Biology, University of California Los Angeles
Peter D. Pioli: Cell and Developmental Biology, University of California Los Angeles
Dan Duan: Cell and Developmental Biology, University of California Los Angeles
Edo Israely: Cell and Developmental Biology, University of California Los Angeles
Daniel Malkin: UCLA
Trent Su: David Geffen School of Medicine at UCLA
Johanna Flach: The Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California San Francisco
Siavash K. Kurdistani: David Geffen School of Medicine at UCLA
Robert H. Schiestl: UCLA
Hanna K. A. Mikkola: Cell and Developmental Biology, University of California Los Angeles

Nature Communications, 2016, vol. 7, issue 1, 1-15

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms12376

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