Open AccessRecombination and transcription of the endogenous Ig heavy chain locus is effected by the Ig heavy chain intronic enhancer core region in the absence of the matrix attachment regions
Author(s) -
Eiko Sakai,
Andrea Bottaro,
Laurie A. Davidson,
Barry P. Sleckman,
Frederick W. Alt
Publication year - 1999
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.96.4.1526
Subject(s) - enhancer , biology , immunoglobulin heavy chain , locus (genetics) , microbiology and biotechnology , scaffold/matrix attachment region , genetics , mutant , gene , complementation , enhancer rnas , transcription (linguistics) , v(d)j recombination , transcription factor , recombination , chromatin remodeling , linguistics , philosophy
The intronic Ig heavy chain (IgH) enhancer, which consists of the core enhancer flanked by 5′ and 3′ matrix attachment regions, has been implicated in control of IgH locus recombination and transcription. To elucidate the regulatory functions of the core enhancer and its associated matrix attachment regions in the endogenous IgH locus, we have introduced targeted deletions of these elements, both individually and in combination, into an IgHa/b -heterozygous embryonic stem cell line. These embryonic stem cells were used to generate chimeric mice by recombination activating gene-2 (Rag-2)-deficient blastocyst complementation, and the effects of the introduced mutations were assayed in mutant B cells. We find that the core enhancer is necessary and sufficient to promote normal variable (V), diversity (D), and joining (J) segment recombination in developing B lineage cells and IgH locus transcription in mature B cells. Surprisingly, the 5′ and 3′ matrix attachment regions were dispensable for these processes.