Stepwise activation of the immunoglobulin μ heavy chain gene locus

D. Chowdhury, R. Sen

Research output: Contribution to journalArticlepeer-review

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 languageEnglish (US)
Pages (from-to)6394-6403
Number of pages10
JournalThe EMBO journal
Volume20
Issue number22
DOIs
StatePublished - Nov 15 2001
Externally publishedYes

Keywords

  • B cells
  • Gene expression
  • Hyperacetylation
  • Immunoglobulin heavy chain

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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