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Molecular and Cellular Biology, August 2006, p. 6117-6129, Vol. 26, No. 16
0270-7306/06/$08.00+0     doi:10.1128/MCB.00642-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Isw1 Functions in Parallel with the NuA4 and Swr1 Complexes in Stress-Induced Gene Repression{dagger}

Kimberly C. Lindstrom,1,2 Jay C. Vary Jr.,1,2 Mark R. Parthun,3 Jeffrey Delrow,4 and Toshio Tsukiyama1*

Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109,1 Molecular and Cellular Biology Program, Fred Hutchinson Cancer Research Center and University of Washington, Seattle, Washington 98195,2 Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, Ohio 43210,3 Genomics Resource, Fred Hutchinson Cancer Research Center, Seattle, Washington 981094

Received 13 April 2006/ Returned for modification 9 May 2006/ Accepted 31 May 2006

The packaging of DNA into chromatin allows eukaryotic cells to organize and compact their genomes but also creates an environment that is generally repressive to nuclear processes that depend upon DNA accessibility. There are several classes of enzymes that modulate the primary structure of chromatin to regulate various DNA-dependent processes. The biochemical activities of the yeast Isw1 ATP-dependent chromatin-remodeling enzyme have been well characterized in vitro, but little is known about how these activities are utilized in vivo. In this work, we sought to discern genetic backgrounds that require Isw1 activity for normal growth. We identified a three-way genetic interaction among Isw1, the NuA4 histone acetyltransferase complex, and the Swr1 histone replacement complex. Transcription microarray analysis revealed parallel functions for these three chromatin-modifying factors in the regulation of TATA-containing genes, including the repression of a large number of stress-induced genes under normal growth conditions. In contrast to a recruitment-based model, we find that the NuA4 and Swr1 complexes act throughout the genome while only a specific subset of the genome shows alterations in transcription.

* Corresponding author. Mailing address: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109. Phone: (206) 667-4996. Fax: (206) 667-6497. E-mail: ttsukiya{at}fhcrc.org.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, August 2006, p. 6117-6129, Vol. 26, No. 16
0270-7306/06/$08.00+0     doi:10.1128/MCB.00642-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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