Distinct Requirements of CHD4 during B Cell Development and Antibody Response

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 m...

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Detalles Bibliográficos
Autores principales: Yen, Wei-Feng, Sharma, Rahul, Cols, Montserrat, Lau, Colleen M., Chaudhry, Ashutosh, Chowdhury, Priyanka, Yewdell, William T., Vaidyanathan, Bharat, Sun, Amy, Coffre, Maryaline, Pucella, Joseph N., Chen, Chun-Chin, Jasin, Maria, Sun, Joseph C., Rudensky, Alexander Y., Koralov, Sergei B., Chaudhuri, Jayanta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2019
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6527137/
https://www.ncbi.nlm.nih.gov/pubmed/31042474
http://dx.doi.org/10.1016/j.celrep.2019.04.011
Descripción
Sumario: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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