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Blood, 1 January 2007, Vol. 109, No. 1, pp. 159-167. Prepublished online as a Blood First Edition Paper on September 12, 2006; DOI 10.1182/blood-2006-02-005355. This Article Full Text (PDF) Supplemental Table, Figures, and Methods All Versions of this Article: blood-2006-02-005355v1 109/1/159    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Laurencikiene, J. Articles by Severinson, E. Search for Related Content PubMed PubMed Citation Articles by Laurencikiene, J. Articles by Severinson, E. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 22, 2006 Accepted August 16, 2006 Regulation of germline transcription and switch region mutations by IgH locus 3' enhancers in transgenic mice Jurga Laurencikiene, Vytas Tamosiunas, and Eva Severinson* Dept of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden Institute of Immunology at Vilnius University, Vilnius, Lithuania * Corresponding author; email: eva.severinson{at}ki.se. Germline (GL) transcription is regulated by specific promoters and Immunoglobulin heavy chain (IgH) 3' locus enhancers and is necessary for Ig class switch recombination (CSR). We have generated different transgenic lines containing the GL promoter, switch (S) region and constant (C) region with or without the HS3A-HS1,2 or HS3B-HS4 3' IgH enhancer pairs. The enhancerless construct was expressed in B cells activated by interleukin (IL)-4 and cluster of differentiation (CD)40, thus resembling regulation of the endogenous gene. Both enhancer containing transgenes efficiently increased expression in B cells and were strongly up-regulated by stimuli. In addition, S regions of the transgene containing HS3B-HS4 were mutated in activated, sorted B cells. Such mutations are known to precede CSR and are dependent on activation induced cytidine deaminase (AID). Our findings show that all elements necessary for recruitment of the recombination machinery are present in the transgene containing HS3 and HS4. These enhancers probably provide something more specific than mere increased accessibility of switch regions. We propose that transcription factors binding the enhancers help to target the recombination machinery to the switch regions. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: W. A. Dunnick, J. T. Collins, J. Shi, G. Westfield, C. Fontaine, P. Hakimpour, and F. N. Papavasiliou Switch recombination and somatic hypermutation are controlled by the heavy chain 3' enhancer region J. Exp. Med., November 23, 2009; 206(12): 2613 - 2623. [Abstract] [Full Text] [PDF] V. Truffinet, E. Pinaud, N. Cogne, B. Petit, L. Guglielmi, M. Cogne, and Y. Denizot The 3' IgH Locus Control Region Is Sufficient to Deregulate a c-myc Transgene and Promote Mature B Cell Malignancies with a Predominant Burkitt-Like Phenotype J. Immunol., November 1, 2007; 179(9): 6033 - 6042. [Abstract] [Full Text] [PDF]

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