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. |