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J. Biol. Chem., Vol. 280, Issue 50, 41207-41212, December 16, 2005

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A Mammalian Chromatin Remodeling Complex with Similarities to the Yeast INO80 Complex^*

Jingji Jin1, Yong Cai1, Tingting Yao, Aaron J. Gottschalk, Laurence Florens, Selene K. Swanson, José L. Gutiérrez, Michael K. Coleman, Jerry L. Workman, Arcady Mushegian¶, Michael P. Washburn, Ronald C. Conaway, and Joan Weliky Conaway||2

From the Stowers Institute for Medical Research, Kansas City, Missouri 64110, the Departments of Biochemistry and Molecular Biology and ^¶Microbiology, Molecular Genetics, and Immunology, Kansas University Medical Center, Kansas City, Kansas 66160, and the ^||Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73190

The mammalian Tip49a and Tip49b proteins belong to an evolutionarily conserved family of AAA⁺ ATPases. In Saccharomyces cerevisiae, orthologs of Tip49a and Tip49b, called Rvb1 and Rvb2, respectively, are subunits of two distinct ATP-dependent chromatin remodeling complexes, SWR1 and INO80. We recently demonstrated that the mammalian Tip49a and Tip49b proteins are integral subunits of a chromatin remodeling complex bearing striking similarities to the S. cerevisiae SWR1 complex (Cai, Y., Jin, J., Florens, L., Swanson, S. K., Kusch, T., Li, B., Workman, J. L., Washburn, M. P., Conaway, R. C., and Conaway, J. W. (2005) J. Biol. Chem. 280, 13665–13670). In this report, we identify a new mammalian Tip49a- and Tip49b-containing ATP-dependent chromatin remodeling complex, which includes orthologs of 8 of the 15 subunits of the S. cerevisiae INO80 chromatin remodeling complex as well as at least five additional subunits unique to the human INO80 (hINO80) complex. Finally, we demonstrate that, similar to the yeast INO80 complex, the hINO80 complex exhibits DNA- and nucleosome-activated ATPase activity and catalyzes ATP-dependent nucleosome sliding.

Received for publication, August 18, 2005 , and in revised form, October 11, 2005.

^* This work was supported by National Institutes of Health Grants R37GM41628 (to R. C. C.) and R37GM47867 (to J. L. W.) and by Grant 5437-05 from the Leukemia and Lymphoma Society (to T. Y.). 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 These authors contributed equally to this work.

² To whom correspondence should be addressed. Tel.: 816-926-4091; Fax: 816-926-2093; E-mail: jlc{at}stowers-institute.org.

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