Abstract
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 DFL16.1, the 5′-most DH gene segment, to the intergenic region between Cμ and Cδ. Germline VH genes were not hyperacetylated at this stage, which accounts for DH to JH, recombination occurring first during B-cell development. Subsequent activation of the VH 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′ VH genes, which are hyperacetylated in response to DJH recombination. These observations lead to mechanisms for two well-documented phenomena in B-cell ontogeny: the sequential rearrangement of DH followed by VH gene segments, and the preferential recombination of DH-proximal VH 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.
Original language | English (US) |
---|---|
Pages (from-to) | 6394-6403 |
Number of pages | 10 |
Journal | The EMBO journal |
Volume | 20 |
Issue number | 22 |
DOIs | |
State | Published - Nov 15 2001 |
Externally published | Yes |
Keywords
- B cells
- Gene expression
- Hyperacetylation
- Immunoglobulin heavy chain
ASJC Scopus subject areas
- Genetics
- Cell Biology