HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dunnick, W. A. Articles by Collins, J. T. Search for Related Content PubMed PubMed Citation Articles by Dunnick, W. A. Articles by Collins, J. T.

Germline Transcription and Switch Recombination of a Transgene Containing the Entire H Chain Constant Region Locus: Effect of a Mutation in a STAT6 Binding Site in the 1 Promoter¹

Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109

The switch (S) in H chain class is preceded by germline transcription and then mediated by a DNA recombination event. One of the impediments toward understanding the mechanism is the lack of a system in which a recombinant DNA molecule undergoes cytokine-regulated class S recombination. To study class S recombination, we used transgenic mice with a 230-kb bacterial artificial chromosome that included a rearranged VDJ gene and the entire murine H chain constant region locus. We found that both germline transcription and S recombination to the transgenic 1 H chain gene were regulated by IL-4 like that of the endogenous genes. In mice with two or more copies of the H chain locus transgene, both germline transcripts and S recombination took place at levels comparable to those from the endogenous loci. We also prepared a version of the transgene with a 4-bp mutation in a STAT6 binding site in the 1 promoter region. On the average, this mutation reduced germline transcription by 80%, but did not change the amount of S recombination in vitro. Among both the wild-type and mutant transgenes, we found no significant correlation between the amount of germline transcripts and the amount of S recombination. We infer that the physiologic level of germline transcription of the 1 gene is in excess over the amount required for efficient S recombination.

This article has been cited by other articles:

				B. Zhang, A. Alaie-Petrillo, M. Kon, F. Li, and L. A. Eckhardt Transcription of a Productively Rearranged Ig VDJC{alpha} Does Not Require the Presence of HS4 in the Igh 3' Regulatory Region J. Immunol., May 15, 2007; 178(10): 6297 - 6306. [Abstract] [Full Text] [PDF]

				J. S. Rush, M. Liu, V. H. Odegard, S. Unniraman, and D. G. Schatz Expression of activation-induced cytidine deaminase is regulated by cell division, providing a mechanistic basis for division-linked class switch recombination PNAS, September 13, 2005; 102(37): 13242 - 13247. [Abstract] [Full Text] [PDF]

				W. A. Dunnick, J. Shi, K. A. Graves, and J. T. Collins The 3' end of the heavy chain constant region locus enhances germline transcription and switch recombination of the four {gamma} genes J. Exp. Med., May 2, 2005; 201(9): 1459 - 1466. [Abstract] [Full Text] [PDF]

				N. Gao, T. Dang, W. A. Dunnick, J. T. Collins, B. R. Blazar, and D. Yuan Receptors and Counterreceptors Involved in NK-B Cell Interactions J. Immunol., April 1, 2005; 174(7): 4113 - 4119. [Abstract] [Full Text] [PDF]

				A. A. Zarrin, M. Tian, J. Wang, T. Borjeson, and F. W. Alt Influence of switch region length on immunoglobulin class switch recombination PNAS, February 15, 2005; 102(7): 2466 - 2470. [Abstract] [Full Text] [PDF]