期刊
INTERNATIONAL IMMUNOLOGY
卷 13, 期 8, 页码 1003-1012出版社
OXFORD UNIV PRESS
DOI: 10.1093/intimm/13.8.1003
关键词
antibodies; B lymphocytes; gene regulation; molecular biology
类别
资金
- NCRR NIH HHS [RR-03037] Funding Source: Medline
- NIAID NIH HHS [AI-30653, R01 AI030653-11] Funding Source: Medline
The Ig heavy chain (IgH) locus is controlled by multiple regulatory sequences mapping both within the IgH transcription unit (E mu) and downstream (3') of IgH coding sequences (hs3a, hs1,2, hs3b and hs4). Enhancer knockout studies in mice have implicated E mu in the control of IgH variable region gene assembly, but single-enhancer knockouts involving the 3' IgH enhancers have yet to shed light on their function. Transfection studies in mice and cell lines have suggested that the 3' enhancers behave similarly to a locus control region as first identified in the beta -globin locus. We have exploited this property to form mini-loci in a surface Ig(+) and an Ig-secreting cell line as a means for studying the functions of the 3' IgH enhancers. Importantly, this experimental system allows for the analysis of enhancer function within the context of chromatin. The mini-loci consisted of an Ig gamma 2b transcription unit linked to the four murine 3' IgH enhancers. Using targeted deletions of enhancer pairs within these mini-loci, we have discovered a critical and apparently developmentally regulated role for the hs3b/hs4 enhancer pair in IgH transgene expression.
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