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The Tor Pathway Regulates Gene Expression by Linking Nutrient Sensing to Histone Acetylation
John R. Rohde and Maria E. Cardenas*
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710
Received for publication 6 September 2002.
Revision received 22 October 2002.
Accepted for publication 25 October 2002.
Abstract:
The Tor pathway mediates cell growth in response to nutrientavailability, in part by inducing ribosomal protein (RP) geneexpression via an unknown mechanism. Expression of RP genescoincides with recruitment of the Esa1 histone acetylase toRP gene promoters. We show that inhibition of Tor with rapamycinreleases Esa1 from RP gene promoters and leads to histone H4deacetylation without affecting promoter occupancy by Rap1 andAbf1. Genetic and biochemical evidence identifies Rpd3 as themajor histone deacetylase responsible for reversing histoneH4 acetylation at RP gene promoters in response to Tor inhibitionby rapamycin or nutrient limitation. Our results illustratethat the Tor pathway links nutrient sensing with histone acetylationto control RP gene expression and cell growth.
* Corresponding author. Mailing address: Department of Molecular Genetics and Microbiology, Duke University Medical Center, 322 CARL Bldg., Box 3546, Research Dr., Durham, NC 27710. Phone: (919) 684-2809. Fax: (919) 684-5458. E-mail: carde004{at}mc.duke.edu.
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