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Publication : Distinct Requirements of CHD4 during B Cell Development and Antibody Response.

First Author  Yen WF Year  2019
Journal  Cell Rep Volume  27
Issue  5 Pages  1472-1486.e5
PubMed ID  31042474 Mgi Jnum  J:281831
Mgi Id  MGI:6380736 Doi  10.1016/j.celrep.2019.04.011
Citation  Yen WF, et al. (2019) Distinct Requirements of CHD4 during B Cell Development and Antibody Response. Cell Rep 27(5):1472-1486.e5
abstractText  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.
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