Recombination 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.

Proc Natl Acad Sci U S A 1999 Feb;96(4):1526-31

The Center for Blood Research, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.

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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC15504PMC
http://dx.doi.org/10.1073/pnas.96.4.1526DOI Listing
February 1999

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References

(Supplied by CrossRef)

Banerji et al.
Cell 1983

Gillies et al.
Cell 1983

Birshtein et al.
Current topics in microbiology and immunology 1997

Garcia et al.
Nature; Physical Science (London) 1986

Grosschedl et al.
Cell 1984

Grosschedl et al.
Cell 1985

Nelsen et al.
International review of cytology 1992

Staudt et al.
Annual review of immunology 1991

Alt et al.
Nature; Physical Science (London) 1982

Burrows et al.
Nature; Physical Science (London) 1983

Aguilera et al.
The EMBO Journal 1985

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