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Stepwise activation of the immunoglobulin μ heavy chain gene locus
Author(s) -
Chowdhury Dipanjan,
Sen Ranjan
Publication year - 2001
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/20.22.6394
Subject(s) - biology , locus (genetics) , gene , v(d)j recombination , microbiology and biotechnology , histone , immunoglobulin heavy chain , germline , gene rearrangement , genetics , recombination
The immunoglobulin heavy chain (IgH) gene locus spans several megabases. We show that IgH activation during B‐cell differentiation, as measured by histone acetylation, occurs in discrete, independently regulated domains. Initially, a 120 kb domain of germline DNA is hyperacetylated, that extends from D FL16.1 , the 5′‐most D H gene segment, to the intergenic region between Cμ and Cδ. Germline V H genes were not hyperacetylated at this stage, which accounts for D H to J H recombination occurring first during B‐cell development. Subsequent activation of the V H locus happens in at least three differentially regulated domains: an interleukin‐7‐regulated domain consisting of the 5′ J558 family, an intermediate domain and the 3′ V H genes, which are hyperacetylated in response to DJ H recombination. These observations lead to mechanisms for two well‐documented phenomena in B‐cell ontogeny: the sequential rearrangement of D H followed by V H gene segments, and the preferential recombination of D H ‐proximal V H genes in pro‐B cells. We suggest that stepwise activation may be a general mechanism by which large segments of the genome are prepared for expression.