Biological Sciences

      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.

      Howe, L., Auston, D., Grant, P., John, S., Cook, R.G., Workman, J.L., and L. Pillus (2001). Histone H3 specific acetyltransferases are essential for cell cycle progression. Genes & Development 15: 3144-3154.

      Garcia, S.N. and Pillus, L. (2002). A unique class of conditional sir2 mutants display distinct silencing defects in Saccharomyces cerevisiae. Genetics 162:721-736.

      Lowell, J.E., A.I. Roughton, V. Lundblad and L. Pillus (2003). Telomerase-independent proliferation is influenced by cell-type in Saccharomyces cerevisiae. Genetics 164: 909-921.

      Jacobson, S., Laurenson, P. and L. Pillus (2004). Functional analysis of chromatin modification in yeast, Methods in Enzymology 377: 3-55(C. Wu and C.D. Allis, eds.).

      Jacobson, S., Laurenson, P. and L. Pillus (2004). Molecular requirements for gene expression mediated by targeted histone acetyltransferases. Mol. Cell. Biol. 24:6029-6039.

      Freeman-Cook, L., E. B. Gomez, E. J. Spedale, J. Marlett, S. L. Forsburg, L. Pillus and P. Laurenson (2005). Conserved locus-specific silencing functions of S. pombe sir2⁺. Genetics 169:1243-1260.

      Lo, W.-S., E.R. Gamache, K.W. Henry, D. Yang, L. Pillus, S.L. Berger (2005). Histone H3 phosphorylation can promote TBP recruitment through distinct promoter-specific mechanisms. EMBO J. 24: 957-1008.

      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.

      Kennedy, E.J. L. Pillus, and and G. Ghosh (2005). Pho5p and newly identified nucleotide pyrophosphatases/phosphodiesterases regulate extracellular nucleotide phosphate metabolism in Saccharomyces cerevisiae. Eukaryotic Cell 4:1892-1902.

      Clarke, A.S., E. Samal and L. Pillus (2006). Distinct roles for the essential MYST family HAT Esa1p in transcriptional silencing. Molec. Biol. Cell. 17:1744-1757.

Lorraine Pillus received her Ph.D. from the Massachusetts Institute of Technology and did postdoctoral research at the University of California, Berkeley, where she was a fellow of the Life Sciences Research Foundation. She has been named a Pew Scholar and a National Science Foundation New Young Investigator.