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

Authors: Wang, Wenyuan; Org, Tonis; Montel-Hagen, Amélie; Pioli, Peter D; Duan, Dan; Israely, Edo; Malkin, Daniel; Su, Trent; Flach, Johanna; Kurdistani, Siavash K; Schiestl, Robert H; Mikkola, Hanna K A

Published In Nat Commun, (2016 08 10)

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.

PubMed ID: 27507714

MeSH Terms: No MeSH terms associated with this publication