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PMID: 9990057 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 96 ·No. 4 ·1999-02-16 ·Pages 1526-31

Sakai E, Bottaro A, Davidson L, Sleckman BP, Alt FW

Abstract

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.

MeSH Terms
Animals B-Lymphocytes/immunology Chimera Crosses, Genetic Embryo, Mammalian Enhancer Elements, Genetic Female Flow Cytometry Genes, Immunoglobulin Heterozygote Immunoglobulin Heavy Chains/genetics Immunoglobulin M/genetics Introns Male Mice Mice, Inbred C57BL Mice, Inbred CBA Recombination, Genetic Regulatory Sequences, Nucleic Acid Restriction Mapping Spleen/immunology Stem Cells Transcription, Genetic Transfection
Chemicals
Immunoglobulin Heavy Chains Immunoglobulin M
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Sakai E
The Center for Blood Research, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
Bottaro A
Davidson L
Sleckman B P
Alt F W
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.96.4.1526
Published
1999-02-16
Pages
1526-31
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC15504
Subset
IM
Grants
PHS HHS · A.I.01297-01 · United States
PHS HHS · A.I.20047 · United States
PHS HHS · A.I.35714 · United States
External Links
PubMed source DOI: 10.1073/pnas.96.4.1526 PMC Full Text View journal details
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