期刊
IMMUNOLOGICAL REVIEWS
卷 305, 期 1, 页码 29-42出版社
WILEY
DOI: 10.1111/imr.13054
关键词
B cell identity; CHD4; chromodomain helicase DNA-binding 4; V(D)J recombination
类别
资金
- NIH [R03AI139822, R01HL127461]
- Wendy Siegel Fund for Leukemia and Cancer Research
- Joe W. and Dorothy Dorsett Brown Foundation
- Victor W. Bolie and Earleen D. Bolie Graduate Scholarship Fund
CHD4 is essential for the development, proliferation, and survival of B cells, as well as for promoting the recombination of the Ig heavy chain and regulating chromatin accessibility, leading to antibody production and mediating humoral immune responses.
B lymphocytes develop from uncommitted precursors into immunoglobulin (antibody)-producing B cells, a major arm of adaptive immunity. Progression of early progenitors to antibody-expressing cells in the bone marrow is orchestrated by the temporal regulation of different gene programs at discrete developmental stages. A major question concerns how B cells control the accessibility of these genes to transcription factors. Research has implicated nucleosome remodeling ATPases as mediators of chromatin accessibility. Here, we describe studies of chromodomain helicase DNA-binding 4 (CHD4; also known as Mi-2 beta) in early B cell development. CHD4 comprises multiple domains that function in nucleosome mobilization and histone binding. CHD4 is a key component of Nucleosome Remodeling and Deacetylase, or NuRD (Mi-2) complexes, which assemble with other proteins that mediate transcriptional repression. We review data demonstrating that CHD4 is necessary for B lineage identity: early B lineage progression, proliferation in response to interleukin-7, responses to DNA damage, and cell survival in vivo. CHD4-NuRD is also required for the Ig heavy-chain repertoire by promoting utilization of distal variable (V-H) gene segments in V(D)J recombination. In conclusion, the regulation of chromatin accessibility by CHD4 is essential for production of antibodies by B cells, which in turn mediate humoral immune responses to pathogens and disease.
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