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MEF2C protects bone marrow B-lymphoid progenitors during stress haematopoiesis

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  • Wenyuan Wang

    (Cell and Developmental Biology, University of California Los Angeles
    Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, UCLA
    Molecular Biology Institute, UCLA)

  • Tonis Org

    (Cell and Developmental Biology, University of California Los Angeles
    Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, UCLA
    Institute of Molecular and Cell Biology, University of Tartu)

  • Amélie Montel-Hagen

    (Cell and Developmental Biology, University of California Los Angeles
    Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, UCLA)

  • Peter D. Pioli

    (Cell and Developmental Biology, University of California Los Angeles
    Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, UCLA)

  • Dan Duan

    (Cell and Developmental Biology, University of California Los Angeles
    Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, UCLA)

  • Edo Israely

    (Cell and Developmental Biology, University of California Los Angeles
    Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, UCLA)

  • Daniel Malkin

    (UCLA
    Jonsson Comprehensive Cancer Center, 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
    Jonsson Comprehensive Cancer Center, UCLA)

  • Hanna K. A. Mikkola

    (Cell and Developmental Biology, University of California Los Angeles
    Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, UCLA
    Molecular Biology Institute, UCLA
    Jonsson Comprehensive Cancer Center, UCLA)

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.

Suggested Citation

  • 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 & Hanna K. A. Mikkola, 2016. "MEF2C protects bone marrow B-lymphoid progenitors during stress haematopoiesis," Nature Communications, Nature, vol. 7(1), pages 1-15, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12376
    DOI: 10.1038/ncomms12376
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