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Enhancers1
*
Division of Clinical Immunology, Karolinska Institutet at Huddinge Hospital and Center for Oral Biology, Novum, Huddinge, Sweden;
Department for Cell and Molecular Biology, Umeå University, Umeå, Sweden; and
Division of Therapeutic Proteins, Center for Biologic Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892
The human IgH 3' enhancers, located downstream of each of the two
C
genes, modulate germline (GL) transcription of the IgH genes by
influencing the activity of promoter-enhancer complexes upstream of the
switch and intervening (I) regions. The regulation of GL 1 and 2
promoters by different human 3' enhancer fragments was investigated in
cell lines representing various developmental stages. Both 1HS1,2
and 2HS1,2 fragments show equally strong enhancer activity on the GL
1 and 2 promoters in both orientations when transiently
transfected into a number of mature B cell line (DG75, CL-01, and HS
Sultan). However, there is no activity in a human pre-B cell line
(NALM-6) nor a human T cell line (Jurkat). HS3 shows no enhancer
activity by itself in any of the cell lines, whereas a modest effect is
noted using HS4 in the three mature B cell lines. However, the
combination of the 2HS3-HS1,2-HS4 fragments, which together form a
potential locus control region, displays a markedly stronger enhancer
activity than the individual fragments with a differential effect on
the 1 and 2 promoters as compared with the 
3 promoter. Our
results suggest that the human GL promoter may be regulated by two
independent pathways. One pathway is induced by TGF-ß1
which directs IgA isotype switch through activation of the GL
promoter and no TGF-ß1-responsive elements are present in
the different 3' enhancer fragments. The other route is through the
human 3' enhancer regions that cis-up-regulate the GL
promoter activity in mature B cells.
This article has been cited by other articles:
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V. V. Volgina, M. Kingzette, S.-K. Zhai, and K. L. Knight A Single 3'{alpha} hs1,2 Enhancer in the Rabbit IgH Locus J. Immunol., December 1, 2000; 165(11): 6400 - 6405. [Abstract] [Full Text] [PDF]
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