Yeast Genetics and Molecular Biology 2000
University of Washington
Seattle, Washington USA
July 2000

Name: Clarke, Astrid
Mailing Address: MCDB, University of Colorado, Porter Box 347, Boulder, CO 80309, USA
Email Address: aclarke@biomail.ucsd.edu
Phone & FAX numbers: (858) 822-2443 & (858) 534-0555

#027

MYST family acetyltransferases function in both transcriptional silencing and activation.
Astrid Clarke (1), Sandra Jacobson (2), Eva Samal (3), Darryl Austen (2), Lorraine Pillus (2)
(1) MCDB, University of Colorado, Porter Box 347, Boulder, CO 80309, USA; (2) University of California San Diego, Department of Biology, 9500 Gilman Drive, La Jolla, CA 92093; (3) University of California San Diego, Department of Chemistry and Biochemistry, 9500 Gilman Drive, La Jolla, CA 92093

The three MYST family acetyltransferases of S. cerevisiae, Sas2p, Sas3p, and Esa1p, have distinct roles in gene expression. Sas2p and Sas3p were identified as affecting the silent mating-type loci and/or telomeric reporter genes. In contrast, Esa1p is the only essential member of the family and it is required for cell cycle progression. Esa1p has histone acetyltransferase (HAT) activity and is the catalytic component of the NuA4 complex, which can activate transcription in vitro. Paradoxically, we have recently uncovered a role for Esa1p in rDNA and telomeric silencing, thereby suggesting that Esa1p has a dual function that is context-dependent, or that Esa1p indirectly acts on silencing factors. Consistent with the former possibility, targeting MYST family HATs to a normally silenced region aberrantly activates transcription of a reporter gene. Furthermore, the Esa1p chromo domain, a chromatin targeting motif, is essential for viability. To pursue MYST HAT roles in vivo, we examined genetic interactions with other HATs such as Gcn5p and Hat1p. These studies reveal synthetic lethality between SAS3 and GCN5 mutants, demonstrating that overlapping HAT activities can together support essential functions. The relationship between HAT activity and transcriptional control remains a critical issue, for which the MYST genes provide insights into the dynamic nature of both positive and negative regulation.

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