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

J. Biol. Chem., Vol. 282, Issue 48, 35169-35178, November 30, 2007

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 282/48/35169    most recent M705719200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ju, Z. Articles by Birshtein, B. K. Search for Related Content PubMed PubMed Citation Articles by Ju, Z. Articles by Birshtein, B. K. Social Bookmarking                      What's this?

Evidence for Physical Interaction between the Immunoglobulin Heavy Chain Variable Region and the 3' Regulatory Region^*

From the Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461

B cell-specific expression of immunoglobulin heavy chain (IgH) genes utilizes two cis regulatory regions, the intronic enhancer (Eµ), located in the J_H-Cµ intron, and a complex regulatory region that lies 3' to the IgH gene cluster, 3' RR. We hypothesized that the 3' RR is involved in IgH gene transcription in plasma cells via physical interaction between distal 3' RR enhancers and target V_H sequences, with loop formation by intervening DNA. In support of this hypothesis we report sequence data at DNA recombination breakpoints as evidence for loop formation preceding DNA inversion in a plasma cell line. In addition, using the chromosome conformation capture technique, physical interactions between V_H and 3' RR were analyzed directly and detected in MPC11 plasma cells and variants and normal splenic B cells but not detected in splenic T cells or in non-B cells. V_H-3' RR interactions were present in the absence of Eµ, but when the hs1,2 enhancer was replaced by a Neo^R gene in a variant cell line lacking Eµ, H chain expression was lost, and interactions between V_H and 3' RR and among the 3' RR regulators themselves were severely disrupted. In addition, the chromosome conformation capture technique detected interactions between the myc promoter and 3' RR elements in MPC11, which like other plasmacytomas contains a reciprocal translocation between the c-myc and the IgH locus. In sum, our data support a hypothesis that cis V_H-3' RR and myc-3' RR interactions involve physical interactions between these DNA elements.

Received for publication, July 12, 2007 , and in revised form, October 1, 2007.

^* This work was supported in part by National Institutes of Health Grant AI13509 (to B. K. B.) and Albert Einstein Cancer Grant P30 CA13330. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Table S1 and Figs. S1-S3.

¹ Supported in part by National Institutes of Health 5T32 CA09173.

² Current address: Dept. of Internal Medicine, University of Pittsburgh Medical Center (UPMC McKeesport), 1500 Fifth Ave., McKeesport, PA 15132.

³ Current address: GlaxoSmithKline Biologicals, Research & Development, rue de l'Institut, 89 B-1330, Rixensart, Belgium.

⁴ To whom correspondence and reprint requests should be addressed: Dept. of Cell Biology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461. Tel.: 718-430-2291; Fax: 718-430-8574; E-mail: birshtei{at}aecom.yu.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				C. Vincent-Fabert, V. Truffinet, R. Fiancette, N. Cogne, M. Cogne, and Y. Denizot Ig Synthesis and Class Switching Do Not Require the Presence of the hs4 Enhancer in the 3' IgH Regulatory Region J. Immunol., June 1, 2009; 182(11): 6926 - 6932. [Abstract] [Full Text] [PDF]

				V. Giambra, S. Volpi, A. V. Emelyanov, D. Pflugh, A. L. M. Bothwell, P. Norio, Y. Fan, Z. Ju, A. I. Skoultchi, R. R. Hardy, et al. Pax5 and Linker Histone H1 Coordinate DNA Methylation and Histone Modifications in the 3' Regulatory Region of the Immunoglobulin Heavy Chain Locus Mol. Cell. Biol., October 1, 2008; 28(19): 6123 - 6133. [Abstract] [Full Text] [PDF]

				J. B. Lawrence and C. M. Clemson Gene associations: true romance or chance meeting in a nuclear neighborhood? J. Cell Biol., September 22, 2008; 182(6): 1035 - 1038. [Abstract] [Full Text] [PDF]