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Originally published In Press as doi:10.1074/jbc.M508858200 on February 9, 2006

J. Biol. Chem., Vol. 281, Issue 16, 10839-10848, April 21, 2006
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Differential Transcriptional Regulation by Mouse Single-minded 2s*

Richard P. Metz, Hyeong-Il Kwak, Tanya Gustafson, Brian Laffin, and Weston W. Porter1

From the Department of Integrated Biosciences, College of Veterinary Medicine, Texas A&M University, College Station, Texas 77843-4458

Single-minded 1 and 2 are unique members of the basic helix-loop-helix Per-Arnt-Sim family as they are transcriptional repressors. Here we report the identification and transcriptional characterization of mouse Sim2s, a splice variant of Sim2, which is missing the carboxyl Pro/Ala-rich repressive domain. Sim2s is expressed at high levels in kidney and skeletal muscle; however, the ratio of Sim2 to Sim2s mRNA differs between these tissues. Similar to full-length Sim2, Sim2s interacts with Arnt and to a lesser extent, Arnt2. The effects of Sim2s on transcriptional regulation through hypoxia, dioxin, and central midline response elements are different than that of full-length Sim2. Specifically, Sim2s exerts a less repressive effect on hypoxia-induced gene expression than full-length Sim2, but is just as effective as Sim2 at repressing TCDD-induced gene expression from a dioxin response element. Interestingly, Sim2s bind to and activates expression from a central midline response element-controlled reporter through an Arnt transactivation domain-dependent mechanism. The differences in expression pattern, protein interactions, and transcriptional activities between Sim2 and Sim2s may reflect differential roles each isoform plays during development or in tissue-specific effects on other protein-mediated pathways.


Received for publication, August 11, 2005 , and in revised form, January 12, 2006.

* This work was supported by National Institutes of Health NCI Grant RO1CA111551 (to W. W. P.), a Howard Hughes Predoctoral Fellowship (to T. G.), and National Institutes of Health NIEHS Pilot Project P30ES09106 (to W. W. P.). 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 To whom corresponding should be addressed: MS 4458 Texas A&M University, College Station, TX 77843-4458. Tel.: 979-845-0733; Fax: 979-862-4929; E-mail: wporter{at}cvm.tamu.edu.


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