Chromodomain helicase DNA‐binding 4 (CHD4) regulates early B cell identity and V(D)J recombination*.

Autor: Hagman, James R., Arends, Tessa, Laborda, Curtis, Knapp, Jennifer R., Harmacek, Laura, O'Connor, Brian P.
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Zdroj: Immunological Reviews; Jan2022, Vol. 305 Issue 1, p29-42, 14p
Abstrakt: Summary: 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‐2β) 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 (VH) 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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