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Distinct Requirements of CHD4 during B Cell Development and Antibody Response.
- Source :
-
Cell reports [Cell Rep] 2019 Apr 30; Vol. 27 (5), pp. 1472-1486.e5. - Publication Year :
- 2019
-
Abstract
- The immunoglobulin heavy chain (Igh) locus features a dynamic chromatin landscape to promote class switch recombination (CSR), yet the mechanisms that regulate this landscape remain poorly understood. CHD4, a component of the chromatin remodeling NuRD complex, directly binds H3K9me3, an epigenetic mark present at the Igh locus during CSR. We find that CHD4 is essential for early B cell development but is dispensable for the homeostatic maintenance of mature, naive B cells. However, loss of CHD4 in mature B cells impairs CSR because of suboptimal targeting of AID to the Igh locus. Additionally, we find that CHD4 represses p53 expression to promote B cell proliferation. This work reveals distinct roles for CHD4 in B cell development and CSR and links the H3K9me3 epigenetic mark with AID recruitment to the Igh locus.<br /> (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
B-Lymphocytes cytology
B-Lymphocytes physiology
Cell Differentiation
Cells, Cultured
Chromatin Assembly and Disassembly
DNA Helicases metabolism
Genes, Immunoglobulin Heavy Chain
Mice
Tumor Suppressor Protein p53 genetics
Tumor Suppressor Protein p53 metabolism
B-Lymphocytes immunology
Cell Proliferation
DNA Helicases genetics
Immunoglobulin Class Switching
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 27
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 31042474
- Full Text :
- https://doi.org/10.1016/j.celrep.2019.04.011