Distinct requirements of CHD4 during B cell development and antibody response Journal Article
| Authors: | Yen, W. F.; Sharma, R.; Cols, M.; Lau, C. M.; Chaudhry, A.; Chowdhury, P.; Yewdell, W. T.; Vaidyanathan, B.; Sun, A.; Coffre, M.; Pucella, J. N.; Chen, C. C.; Jasin, M.; Sun, J. C.; Rudensky, A. Y.; Koralov, S. B.; Chaudhuri, J. |
| Article Title: | Distinct requirements of CHD4 during B cell development and antibody response |
| 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. Yen et al. demonstrate that CHD4, a component of the NuRD remodeling complex, is essential for early B cell development, represses p53 expression in mature B cells, and influences the recruitment of AID to DNA during class switch recombination. © 2019 The Author(s) |
| Keywords: | controlled study; protein expression; unclassified drug; dna binding protein; gene deletion; nonhuman; lymphocyte proliferation; animal cell; mouse; cell maturation; protein depletion; animal experiment; gene locus; protein p53; b lymphocyte; class switch recombination; activation induced cytidine deaminase; immunoglobulin heavy chain; epigenetics; antibody response; immunoglobulin class switching; p53; b lymphocyte differentiation; aid; chromatin remodeling; h3k9me3; male; female; priority journal; article; nurd complex; chd4; germinal centers; chromo domain helicase dna binding protein 4 |
| Journal Title: | Cell Reports |
| Volume: | 27 |
| Issue: | 5 |
| ISSN: | 2211-1247 |
| Publisher: | Cell Press |
| Date Published: | 2019-04-30 |
| Start Page: | 1472 |
| End Page: | 1486.e5 |
| Language: | English |
| DOI: | 10.1016/j.celrep.2019.04.011 |
| PUBMED: | 31042474 |
| PROVIDER: | scopus |
| PMCID: | PMC6527137 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 June 2019 -- Source: Scopus |
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