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Genes & Dev. 25 (9): 984-995

Copyright © 2011 by Cold Spring Harbor Laboratory Press.

Phosphoinositide [PI(3,5)P2] lipid-dependent regulation of the general transcriptional regulator Tup1

Bong-Kwan Han, and Scott D. Emr1

Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA; and Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, New York 14853, USA

Abstract: Transcriptional activity of a gene is governed by transcriptional regulatory complexes that assemble/disassemble on the gene and control the chromatin architecture. How cytoplasmic components influence the assembly/disassembly of transcriptional regulatory complexes is poorly understood. Here we report that the budding yeast Saccharomyces cerevisiae has a chromatin architecture-modulating mechanism that is dependent on the endosomal lipid PI(3,5)P2. We identified Tup1 and Cti6 as new, highly specific PI(3,5)P2 interactors. Tup1—which associates with multiple transcriptional regulators, including the HDAC (histone deacetylase) and SAGA complexes—plays a crucial role in determining an activated or repressed chromatin state of numerous genes, including GAL1. We show that, in the context that the Gal4 activation pathway is compromised, PI(3,5)P2 plays an essential role in converting the Tup1-driven repressed chromatin structure into a SAGA-containing activated chromatin structure at the GAL1 promoter. Biochemical and cell biological experiments suggest that PI(3,5)P2 recruits Cti6 and the Cyc8–Tup1 corepressor complex to the late endosomal/vacuolar membrane and mediates the assembly of a Cti6–Cyc8–Tup1 coactivator complex that functions to recruit the SAGA complex to the GAL1 promoter. Our findings provide important insights toward understanding how the chromatin architecture and epigenetic status of a gene are regulated by cytoplasmic components.

Key Words: PI(3,5)P2 lipid • Cti6–Cyc8–Tup1 • GAL1 transcriptional induction • lysosomal vacuolar endosome

Received for publication October 2, 2010. Accepted for publication March 8, 2011.

1 Corresponding author.

E-MAIL sde26{at}; FAX (607) 255-5961.

Article is online at

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