Chromodomain helicase DNA-binding 4 (CHD4) regulates early B cell identity and V(D)J recombination.
Immunol Rev
; 305(1): 29-42, 2022 01.
Article
in En
| MEDLINE
| ID: mdl-34927255
ABSTRACT
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-2ß) 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Mi-2 Nucleosome Remodeling and Deacetylase Complex
/
V(D)J Recombination
Limits:
Humans
Language:
En
Journal:
Immunol Rev
Year:
2022
Document type:
Article
Affiliation country: