e-mail: lpillus@ucsd.edu
Lab Homepage: Pillus Lab
A gene's chromosomal position and local chromatin structure can have profound consequences for its expression. We are interested in all aspects of these chromosomal and chromatin effects because they underlie epigenetic processes that are critical for normal growth and development. We are particularly focused on the form of chromatin regulation known as transcriptional silencing and study its effects on yeast and human genes.
Chromatin is controlled by post-translational modification of its core subunits, the histones, and other transcriptional factors. The enzymes catalyzing these modifications include acetyltransferases, (HATs), deacetylases (HDACs), methyltransferases (MTs), kinases, and others. The enzymes work together to promote dynamic patterns of modification that help to specify epigenetic processes. We study several classes of the chromatin modifying enzymes to understand the range of their in vivo functions, including mechanisms of their activity, genomic targeting, and interaction with transcriptional and DNA repair complexes. Our experimental approaches include genetic, genomic and biochemical strategies to understand the MYST family HATs, the SIR2 family HDACs, and several classes of evolutionarily conserved MTs.
Pillus. L. and J. Rine (2005) SIR1 and the origin of epigenetic states in Saccharomyces cerevisiae. Cold Spring Harbor Symposium on Quantitative Biology LXIX: 259-265.
Clarke, A.S., Samal, E., and Pillus, L. (2006) Distinct roles for the essential MYST family HAT Esa1p in transcriptional silencing. Mol. Biol. Cell 17: 1744-1757.
Wilson, J.M., Le, V.Q., Zimmerman, C., Marmorstein, R., and Pillus L (2006) Nuclear export modulates the cytoplasmic Sir2 homologue Hst2 EMBO Reports 7:1247-1251 PMCID: PMC1794688
Ruault, M. and Pillus, L. (2006) Chromatin modifiying enzymes are essential when the Saccharomyces cerevisiae morphogenesis checkpoint is constitutively activated Genetics 174:1135-1149
Lafon A, Chang CS, Scott EM, Jacobson SJ, and Pillus L. (2007) MYST opportunities for growth control: yeast genes illuminate human cancer gene functions. Oncogene. 26:5373-5384. PMID: 17694079
Kennedy, E.J., Ghosh G., and Pillus, L. (2008) Identification of functionally distinct regions that mediate biological activity of the Protein Kinase A homolog TPK2. Journal of Biological Chemistry. 283: 1084-1093 PMID: 17971450
Darst, R.P., Garcia, S.N., Krick, M., and Pillus, L. (2008) Slx5p promotes transcriptional silencing and is required for robust growth in the absence of Sir2p. Molec. Cell. Biol. 28:1361-1372 PMID: 18086879.
Pillus L (2008) MYSTs Mark Chromatin for Chromosomal Functions. Curr. Opin. Cell Biology 20:326-333 PMID: 18511253.