title: MEF2C protects bone marrow B-lymphoid progenitors during stress haematopoiesis.
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.
authors: Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, California 90095, USA.|Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, California 90095, USA.|Molecular Biology Institute, UCLA, Los Angeles, California 90095, USA.
authors: Wenyuan
authors: W
authors: Wang
authors: Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, California 90095, USA.|Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, California 90095, USA.|Institute of Molecular and Cell Biology, University of Tartu, Tartu 51010, Estonia.
authors: Tonis
authors: T
authors: Org
authors: Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, California 90095, USA.|Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, California 90095, USA.
authors: Amélie
authors: A
authors: Montel-Hagen
authors: Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, California 90095, USA.|Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, California 90095, USA.
authors: Peter D
authors: PD
authors: Pioli
authors: Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, California 90095, USA.|Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, California 90095, USA.
authors: Dan
authors: D
authors: Duan
authors: Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, California 90095, USA.|Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, California 90095, USA.
authors: Edo
authors: E
authors: Israely
authors: Department of Molecular Toxicology, UCLA, Los Angeles, California 90095, USA.|Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California 90095, USA.
authors: Daniel
authors: D
authors: Malkin
authors: Department of Biological Chemistry, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA.
authors: Trent
authors: T
authors: Su
authors: The Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California San Francisco, San Francisco, California 94143, USA.
authors: Johanna
authors: J
authors: Flach
authors: Department of Biological Chemistry, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA.
authors: Siavash K
authors: SK
authors: Kurdistani
authors: Department of Molecular Toxicology, UCLA, Los Angeles, California 90095, USA.|Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California 90095, USA.
authors: Robert H
authors: RH
authors: Schiestl
authors: Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, California 90095, USA.|Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, California 90095, USA.|Molecular Biology Institute, UCLA, Los Angeles, California 90095, USA.|Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California 90095, USA.
authors: Hanna K A
authors: HK
authors: Mikkola
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D002843:Chromatin / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D006410:Hematopoiesis / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D064326:MEF2 Transcription Factors / Q000502:physiology; D008297:Male; D051379:Mice; D054448:Precursor Cells, B-Lymphoid / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D060152:V(D)J Recombination / Q000502:physiology*; D014916:Whole-Body Irradiation / Q000009:adverse effects
chemical_list: D002843:Chromatin; D064326:MEF2 Transcription Factors; C578041:Mef2c protein, mouse; D005472:Fluorouracil