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MEF2C protects bone marrow B-lymphoid progenitors during stress haematopoiesis
- 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
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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.
- Subjects :
- 0301 basic medicine
Male
General Physics and Astronomy
chemistry.chemical_compound
Mice
Double-Stranded
2.1 Biological and endogenous factors
DNA Breaks, Double-Stranded
Aetiology
Multidisciplinary
MEF2 Transcription Factors
V(D)J recombination
Chromatin
Cell biology
Haematopoiesis
Female
Stem Cell Research - Nonembryonic - Non-Human
Fluorouracil
Development of treatments and therapeutic interventions
Whole-Body Irradiation
Biotechnology
DNA repair
Cell Survival
Precursor Cells
1.1 Normal biological development and functioning
Science
Biology
General Biochemistry, Genetics and Molecular Biology
Article
03 medical and health sciences
Underpinning research
Genetics
Animals
Progenitor cell
Gene
Transcription factor
B-Lymphoid
5.2 Cellular and gene therapies
Precursor Cells, B-Lymphoid
DNA Breaks
General Chemistry
Stem Cell Research
V(D)J Recombination
Hematopoiesis
030104 developmental biology
chemistry
Immunology
Generic health relevance
DNA
Subjects
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.