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Originally published In Press as doi:10.1074/jbc.M512816200 on April 9, 2006

J. Biol. Chem., Vol. 281, Issue 23, 15735-15740, June 9, 2006
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A High Mobility Group Protein Binds to Long CAG Repeat Tracts and Establishes Their Chromatin Organization in Saccharomyces cerevisiae*Formula

Haeyoung Kim and Dennis M. Livingston1

From the Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota 55455

Long CAG repeat tracts cause human hereditary neurodegenerative diseases and have a propensity to expand during parental passage. Unusual physical properties of CAG repeat tracts are thought to contribute to their instability. We investigated whether their unusual properties alter the organization of CAG repeat tract chromatin. We report that CAG repeat tracts, embedded in yeast chromosomes, have a noncanonical chromatin organization. Digestion of chromatin with the restriction enzyme Fnu4HI reveals hypersensitive sites occurring ~125 bp apart in the repeat tract. To determine whether a non-histone protein establishes this pattern, we performed a yeast one-hybrid screen using CAG repeat tracts embedded in front of two reporter genes. The screen identified the high mobility group box protein Hmo1. Chromatin immunoprecipitation of epitope-tagged Hmo1 selectively precipitates CAG repeat tracts DNAs that range from 26 to 126 repeat units. Moreover, deletion of HMO1 drastically alters the Fnu4HI digestion pattern of CAG repeat chromatin. These results show that Hmo1 binds to CAG repeat tracts in vivo and establish the basis of their novel chromatin organization.


Received for publication, November 30, 2005 , and in revised form, April 5, 2006.

* This work was supported by National Institutes of Health Grant NS41823. 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.

Formula The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. 1–3.

1 To whom correspondence should be addressed: Dept. of Biochemistry, Molecular Biology, and Biophysics, 321 Church St. SE, Minneapolis, MN 55455. Tel.: 612-625-1484: Fax: 612-625-2163: E-mail: livin001{at}umn.edu.


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