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MEF2C protects bone marrow B-lymphoid progenitors during stress haematopoiesis

Authors :
Hanna K. A. Mikkola
Robert H. Schiestl
Johanna Flach
Daniel Malkin
Amélie Montel-Hagen
Dan Duan
Edo Israely
Tonis Org
Trent Su
Peter D. Pioli
Wenyuan Wang
Siavash K. Kurdistani
Source :
Europe PubMed Central, Nature Communications, Vol 7, Iss 1, Pp 1-15 (2016), Nature communications, vol 7, iss 1, Wang, W; Org, T; Montel-Hagen, A; Pioli, PD; Duan, D; Israely, E; et al.(2016). MEF2C protects bone marrow B-lymphoid progenitors during stress haematopoiesis. NATURE COMMUNICATIONS, 7. doi: 10.1038/ncomms12376. UCLA: Retrieved from: http://www.escholarship.org/uc/item/1xk6z95n, Nature Communications

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.<br />MEF2C is a transcription factor required for B-cell proliferation. Here the authors show that MEF2C is also needed in B-cell development and recovery from stress by inducing expression of DNA repair factors that prevent double stranded breaks and enable VDJ recombination.

Details

Database :
OpenAIRE
Journal :
Europe PubMed Central, Nature Communications, Vol 7, Iss 1, Pp 1-15 (2016), Nature communications, vol 7, iss 1, Wang, W; Org, T; Montel-Hagen, A; Pioli, PD; Duan, D; Israely, E; et al.(2016). MEF2C protects bone marrow B-lymphoid progenitors during stress haematopoiesis. NATURE COMMUNICATIONS, 7. doi: 10.1038/ncomms12376. UCLA: Retrieved from: http://www.escholarship.org/uc/item/1xk6z95n, Nature Communications
Accession number :
edsair.doi.dedup.....b882a3b147b415c63045c4c82078e54c
Full Text :
https://doi.org/10.1038/ncomms12376.