The Journal of Experimental Medicine
Avanti Polar Lipids, Inc.
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 398K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mills, F. C.
Right arrow Articles by Max, E. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mills, F. C.
Right arrow Articles by Max, E. E.
Right arrowPubmed/NCBI databases
*Gene*GEO Profiles
*UniGene
*Compound via MeSH
*Substance via MeSH
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?
© The Rockefeller University Press, 0022-1007/1997/9/845/ $5.00
The Journal of Experimental Medicine, Volume 186, Number 6, September 15, 1997 845-858

Articles

Enhancer Complexes Located Downstream of Both Human Immunoglobulin C{alpha} Genes

Frederick C. Mills, Nagaradona Harindranath, Mary Mitchell, and Edward E. Max

From the Laboratory of Cell and Viral Regulation, Division of Hematologic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892

To investigate regulation of human immunoglobulin heavy chain expression, we have cloned DNA downstream from the two human C{alpha} genes, corresponding to the position in the mouse IgH cluster of a locus control region (LCR) that includes an enhancer which regulates isotype switching. Within 25 kb downstream of both the human immunoglobulin C{alpha}1 and C{alpha}2 genes we identified several segments of DNA which display B lymphoid–specific DNase I hypersensitivity as well as enhancer activity in transient transfections. The corresponding sequences downstream from each of the two human C{alpha} genes are nearly identical to each other. These enhancers are also homologous to three regions which lie in similar positions downstream from the murine C{alpha} gene and form the murine LCR. The strongest enhancers in both mouse and human have been designated HS12. Within a 135-bp core homology region, the human HS12 enhancers are ~90% identical to the murine homolog and include several motifs previously demonstrated to be important for function of the murine enhancer; additional segments of high sequence conservation suggest the possibility of previously unrecognized functional motifs. On the other hand, certain functional elements in the murine enhancer, including a B cell–specific activator protein site, do not appear to be conserved in human HS12. The human homologs of the murine enhancers designated HS3 and HS4 show lower overall sequence conservation, but for at least two of the functional motifs in the murine HS4 (a {kappa}B site and an octamer motif ) the human HS4 homologs are exactly conserved. An additional hypersensitivity site between human HS3 and HS12 in each human locus displays no enhancer activity on its own, but includes a region of high sequence conservation with mouse, suggesting the possibility of another novel functional element.

Address correspondence to Dr. Frederick C. Mills, Division of Hematologic Products, FDA/CBER/HFM-541, Bldg. 29A, RM 2B09, 29 Lincoln Dr., MSC 4555, Bethesda, MD 20892-4555. Phone: 301-827-1808; FAX: 301-480-3256; E-mail: millsf{at}fdacb.cber.fda.gov

Note added in proof. While this manuscript was under review, related investigations by two other laboratories came to our attention. Chen, C., and B.K. Birshtein (1997. J. Immunol. 159:1310–1318.) have described the HS12 enhancers from the {alpha}1 and {alpha}2 loci; and recently others have characterized the HS3 and HS12 enhancers from the {alpha}1 locus (M. Cogné, personal communication).

F.C. Mills and N. Harindranath both made substantial contributions to this work.

1 Abbreviations used in this paper: BAC, bacterial artificial chromosome; BSAP, B cell–specific activator protein; HSE, heat shock element; HSTF, heat shock transcription factors; LCR, locus control region.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS