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  4. Lorraine Pillus

Lorraine Pillus

Research

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.

Select Publications

  • Petty, E.L. and Pillus, L. (2021) Cell cycle roles for GCN5 revealed through genetic suppression. BBA Gene Regulatory Mechanisms, special issue in honor of Susan Abmayr Biochim Biophys Acta Gene Regul Mech1864:194625. doi: 10.1016/j.bbagrm.2020.194625. PMID: 32798737
  • Li, Y., Jiang, Y., Paxman, J., O’Laughlin, R., Pillus, L. Tsimring, L.V. Hasty, J. and Hao, N. J (2020) A programmable fate decision underlies single-cell aging in yeast. Science 369: 325-329 PMID: 32675375
  • Jin, M., Li, Y., O’Laughlin, R., Bitthin, P., Pillus, L., Tsimring, L., Hasty, J. and Hao, N. (2019) Divergent aging of isogenic yeast cells revealed through single-cell phenotypic dynamics. Cell Systems 8: 242-253 PMID: 30852250
  • Petty, E.L., Evpak, M, and Pillus, L. (2018) Connecting GCN5’s centromeric SAGA to the mitotic tension-sensing checkpoint Mol. Biol. Cell 29: 2201-2212 PMID: 29995571
  • Searle NE and Pillus L. (2018) Critical genomic regulation mediated by Enhancer of Polycomb Current Genetics 64:147-154 PMID: 28884217
  • Li Y, Jin M, O'Laughlin R, Bittihn P, Tsimring LS, Pillus L, Hasty J, Hao N (2017) Multi-generational silencing dynamics control cell aging. Proc Natl Acad Sci, USA 114:11253-11258 PMID: 29073021
  • Mason AG, Garza RM, McCormick MA, Patel B, Kennedy BK, Pillus L, La Spada AR (2017)The replicative lifespan-extending deletion of SGF73 results in altered ribosomal gene expression in yeast. Aging Cell 16(4):785-796 PMID: 28568901
  • Searle NE, Torres-Machorro AL, Pillus L. (2017) Chromatin Regulation by the NuA4 Acetyltransferase Complex Is Mediated by Essential Interactions Between Enhancer of Polycomb (Epl1) and Esa1. Highlighted in Genetics. 205:1125-1137. PMID: 28108589
  • Petty EL, Lafon A, Tomlinson SL, Mendelsohn BA, Pillus L. (2016) Promotion of Cell Viability and Histone Gene Expression by the Acetyltransferase Gcn5 and the Protein Phosphatase PP2A in Saccharomyces cerevisiae. Genetics 203:1693-707. PMID: 27317677
  • Su, XB and Pillus, L. (2016) Functions for diverse metabolic activities in heterochromatin. Proceedings of the National Academies of Sciences, USA. doi: 10.1073/pnas.1518707113.
  • Torres-Machorro AL, Clark LG, Chang CS, Pillus L. (2015) The Set3 Complex Antagonizes the MYST Acetyltransferase Esa1 in the DNA Damage Response. doi: 10.1073/pnas.1518707113.
  • Torres-Machorro AL, Aris JP, Pillus L. (2015) A moonlighting metabolic protein influences repair at DNA double-stranded breaks. Nucleic Acids Res. 2015 43:1646-1658. PMID: 25628362.
  • Basnet H, Su XB, Tan Y, Meisenhelder J, Merkurjev D, Ohgi KA, Hunter T, *Pillus L, *Rosenfeld MG (2014) Tyrosine phosphorylation of histone H2A by CK2 regulates transcriptional elongation.Nature 516:267-71. PMID: 25252977
  • McCormick MA, Mason AG, Guyenet SJ, Dang W, Garza RM, Ting MK, Moller RM, Berger SL, Kaeberlein M, Pillus L, La Spada AR, Kennedy BK (2014) The SAGA histone deubiquitinase module controls yeast replicative lifespan via Sir2 interaction. Cell Reports 8:477-86. PMID: 25043177.
  • Torres-Machorro AL, Pillus L. (2014) Bypassing the Requirement for an Essential MYST Acetyltransferase. Genetics 197:851-863. PMID: 24831819
  • Eustice M, Pillus L. (2014) Unexpected function of the glucanosyltransferase Gas1 in the DNA damage response linked to histone H3 acetyltransferases in Saccharomyces cerevisiae. Genetics 196:1029-39. PMID: 24532730
  • Petty E, Pillus L. (2013) Balancing chromatin remodeling and histone modifications in transcription. Trends in Genetics 29:621-9. PMID: 23870137
  • Chen, M., Licon, K., Otsuka, R., Pillus, L. and Ideker, T. (2013) Decoupling chromatin and genetic effects through systematic analysis of gene position. Cell Reports 3(1):128-37. PMID:23291096
  • Chang, C.S., Clarke, A.S. and Pillus, L. (2012) Suppression analysis of esa1 mutants in S. cerevisiae links NAB3 to transcriptional silencing and nucleolar functions G3: Genes, Genomes, Genetics 2(10):1223-32.PMID: 23050233
  • Lafon, A., Petty, E. and Pillus, L. (2012) Functional antagonism between Sas3 and Gcn5 acetyltransferases and ISWI chromatin remodelers PLoS Genetics 8(10):e1002994. PMID: 23055944.
  • Garza, R. and Pillus, L. (2012) STUbLs in chromatin and genome stability. 99(2):146-54 PMID: 23175389
  • Scott, E.M. and Pilllus, L. (2010) Homocitrate synthase connects amino acid metabolism to chromatin functions through Esal and DNA damage.Genes & Development 24:1903-1913 PMID: 20810648.
  • Jacobson, S. and Pillus, L. (2009) The SAGA subunit Ada2 functions in transcriptional silencing. Molecular and Cellular Biology29:6033-6045.
  • Chang, C.S. and Pillus, L. (2009) Collaboration Between the Essential Esa1 acetyltransferase and the Rpd3 Deacetylase is Mediated by H4K12 Histone Acetylation in Saccharomyces cerevisiae. Genetics 183:149-160 PMID: 19596907.
  • Koch, M.R. and Pillus, L. (2009) The Gas1 Glucanosyltransferase functions in transcriptional silencing. Proceedings of the National Academy of Sciences 106:11224-11229. PMID: 19541632.
  • Mak, H.C., Pillus, L., and Ideker, T. (2009) Dynamic reprogramming of transcription factors to and from the subtelomere. Genome Research 9:1014-25 PMID: 19372386.
  • Koch, M.R. and Pillus, L. (2009) Silent chromatin formation and regulation in the yeast Saccharomyces cerevisiae. Handbook of Cell Signaling, 2nd Edition, Oxford: Academic Press eds., R. Bradshaw and E. Dennis, pp. 2427-2436.
  • 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.
  • 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.
  • 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.

Biography

Lorraine Pillus carried out graduate studies with Frank Solomon at MIT. Her postdoctoral research with Jasper Rine at the University of California, Berkeley was supported by a John D. and Catherine T. MacArthur Foundation Fellowship of the Life Sciences Research Foundation. Prof. Pillus has been named a Pew Scholar and a National Science Foundation New Young Investigator and has received teaching excellence awards from the Mortar Board Honor Society and the Associated Students of the Skaggs School of Pharmacy & Pharmaceutical Sciences. She served as Chair of Molecular Biology from 2012 – 2016 and Associate Dean of the Division from 2016 – 2019. She was elected as a Fellow of the American Association for the Advancement of Science in 2017, to the American Academy of Microbiology in 2018, and named a Revelle College Faculty Fellow in 2020.

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