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Divergent Roles of RelA and c-Rel in Establishing Chromosomal Loops upon Activation of the Ig Gene¹

Zhe Liu^*,, Zhenyi Ma, Lance S. Terada and William T. Garrard^2,*

^* Department of Molecular Biology and Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390; and Research Center of Basic Medical Sciences, Department of Immunology, Tianjin Medical University, Tianjin, People’s Republic of China

Precise regulation of eukaryotic gene expression requires interactions between distal cis-acting regulatory sequences with the looping out of the intervening DNA, but how trans-acting regulatory proteins work to establish and maintain DNA loops during gene activation remains largely unexplored. LPS-induced transcription of the mouse Ig gene in B lymphocytes utilizes three distal enhancers and requires the transcription factor NF-B, whose family members include RelA and c-Rel. Using chromosome conformation capture technology in combination with chromatin immunoprecipitation, here we demonstrate that LPS-induced Ig gene activation creates chromosomal loops by bridging together all three pairwise interactions between the distal enhancers and RNA polymerase II, the apparent molecular tie for the bases of these loops. RelA and actin polymerization are essential for triggering these processes, which do not require new transcription, protein synthesis, or c-Rel. We have thus identified both essential and nonessential events that establish higher order chromatin reorganization during Ig gene activation.

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.

¹ This investigation was supported by National Institutes of Health Grants GM29935 and AI067906 and Grant I-823 from the Robert A. Welch Foundation (to W.T.G.), and by National Institutes of Health Grants HL067256 and HL61897 (to L.S.T.).

² Address correspondence and reprint requests to Dr. William T. Garrard, Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390. E-mail address: william.garrard{at}utsouthwestern.edu

³ Abbreviations used in this paper: Ei, intronic enhancer; BDM, 2,3-butanedione monoxime; ChIP, chromatin immunoprecipitation; PBGD, porphobilinogen deaminase; Pol II, RNA polymerase II; shRNA, short hairpin RNA; 3C, chromosome conformation capture technology.

⁴ The online version of this article contains supplemental material.

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The JI 2009 183: 3557-3558. [Full Text]