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
Notes: Article -- Export Date: 3 June 2019 -- Source: Scopus
Citation Impact
MSK Authors
  1. Maria Jasin
    242 Jasin
  2. Alexander Rudensky
    144 Rudensky
  3. Joseph C Sun
    104 Sun
  4. Wei-Feng Yen
    12 Yen
  5. Chun-Chin   Chen
    6 Chen
  6. William Theodore Yewdell
    16 Yewdell
  7. Rahul Sharma
    5 Sharma
  8. Colleen M Lau
    22 Lau