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Dyad symmetry within the mouse 3' IgH regulatory region includes two virtually identical enhancers (C alpha3'E and hs3).

S Saleque, M Singh, R D Little, S L Giannini, J S Michaelson and B K Birshtein
J Immunol May 15, 1997, 158 (10) 4780-4787;
S Saleque
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M Singh
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R D Little
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S L Giannini
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J S Michaelson
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B K Birshtein
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Abstract

The transcription of the murine Ig heavy chain locus is regulated not only by the intronic enhancer, E mu, but also by a 3' regulatory region located downstream of the C alpha membrane exon. Several DNase I-hypersensitive sites (hs1-4) and enhancer elements (e.g., C alpha3'E) have been identified in this 3' regulatory region, and some of these were suggested to comprise a locus control region. However, little is known about the coordinate regulation or function of these individual elements. Here we provide evidence that C alpha3'E and hs3 are virtually mirror images of each other and demarcate the edges of an approximately 25-kb region of quasi-dyad symmetry with 3'alphaE(hs1,2) at its center. Flanking 3'alphaE(hs1,2) are inverted repeats and families of repetitive sequences uniquely located in this region. We have observed that, like 3'alphaE(hs1,2) and hs3, C alpha3'E is DNase I hypersensitive in plasma cell lines, but not in a pre-B cell line. Additionally, we found that C alpha3'E and hs3 show significant transcriptional synergy in transfection assays only in a plasma cell line. The DNA topology of the 3' regulatory region coupled with new and existing data on the activity of its individual enhancers during B cell differentiation lead us to propose a biphasic model for the activity of this region. According to our model, one unit, consisting of the 3'-most enhancer, hs4, is active early and throughout B cell development. The second unit, which comprises C alpha3'E, 3'alphaE(hs1,2), and hs3, becomes active later in development, when it contributes to such processes as class switching and increased levels of Ig heavy chain gene transcription in plasma cells.

  • Copyright © 1997 by American Association of Immunologists

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The Journal of Immunology
Vol. 158, Issue 10
15 May 1997
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Dyad symmetry within the mouse 3' IgH regulatory region includes two virtually identical enhancers (C alpha3'E and hs3).
S Saleque, M Singh, R D Little, S L Giannini, J S Michaelson, B K Birshtein
The Journal of Immunology May 15, 1997, 158 (10) 4780-4787;

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Dyad symmetry within the mouse 3' IgH regulatory region includes two virtually identical enhancers (C alpha3'E and hs3).
S Saleque, M Singh, R D Little, S L Giannini, J S Michaelson, B K Birshtein
The Journal of Immunology May 15, 1997, 158 (10) 4780-4787;
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Print ISSN 0022-1767        Online ISSN 1550-6606