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Originally published In Press as doi:10.1074/jbc.M409415200 on September 27, 2004
J. Biol. Chem., Vol. 279, Issue 50, 51862-51868, December 10, 2004
Nuclear Matrix Interactions at the Human Protamine Domain
A WORKING MODEL OF POTENTIATION*
Rui Pires Martins ,
G. Charles Ostermeier , and
Stephen A. Krawetz ¶||
From the
Center for Molecular Medicine and Genetics, the Department of Obstetrics and Gynecology, and the ¶Institute for Scientific Computing, Wayne State University, School of Medicine, Detroit, Michigan 48201
The compact eukaryotic genome must be selectively opened to grant trans-factor access to cis-regulatory elements to overcome the primary barrier to gene transcription. The mechanism that governs the selective opening of chromatin domains (i.e. potentiation) remains poorly understood. In the absence of a well defined locus control region, the nuclear matrix is considered the primary candidate regulating the opening of the multigenic PRM1 PRM2 TNP2 human protamine domain. To directly examine its role, four lines of transgenic mice with different configurations of flanking nuclear matrix attachment regions (MARs) encompassing the protamine domain were created. We show that upon removal of the MARs, the locus becomes subject to position effects. The 3' MAR alone may be sufficient to protect against silencing. In concert, the MARs bounding this domain likely synergize to regulate the expression of the various members of this gene cluster. Interestingly, the MARs may convey a selective reproductive advantage, such that constructs bearing both 5' and 3' MARs are passed to their offspring with greater frequency. Thus, the MARs bounding the PRM1 PRM2 TNP2 protamine domain have many and varied functions.
Received for publication, August 17, 2004
, and in revised form, September 20, 2004.
* This work was supported in part by National Institutes of Health Grant HD36512 (to S. A. K.) and by a predoctoral interdisciplinary biomedical sciences fellowship from the Wayne State University School of Medicine (to R. P. M.). The Transgenic Animal Model Core of the University of Michigan's Biomedical Research Core Facilities was funded in part by the Michigan Economic Development Council. 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.
|| To whom correspondence should be addressed: Dept. of Obstetrics and Gynecology, Molecular Medicine, and Genetics, Institute for Scientific Computing, Wayne State University School of Medicine, 275 E. Hancock, Detroit, MI 48201. Tel.: 313-577-6770; Fax: 313-577-8554; E-mail: steve{at}compbio.med.wayne.edu.

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Copyright © 2004 by the American Society for Biochemistry and Molecular Biology.
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