Faculty and Research Interests
Michael Law, PhD
Science Center, Room 122
University of Southern California, CA
PhD (Biochemistry and Molecular Biology) , 2006
My research is focused on understanding how transcriptional control regulates cell fate decisions. Cells that are presented with an environmental challenge must respond in a manner that is appropriate for the stimulus. Using the budding yeast Saccharomyces cerevisiae as a model system, my work focuses on post-translational histone modifications during metabolic challenge and differentiation. Yeast can undergo two forms of differentiation that are initiated by nutrient limitation, pseudohyphal growth and meiosis. To enter these differentiation pathways, temporal and spatial restrictions on gene expression exist. Histone proteins, which are responsible for packaging DNA in the nucleus, are subject to post-translational modifications such as methylation, acetylation, phosphorylation, and ubiquitylation. Different combinations of these modifications provide a “histone code” that allows an intricate and coordinated execution of gene transcription programs, regulating transcriptional activation and repression. While much is known about how the histone code acts to influence transcription, much less is known regarding how the enzymes responsible for writing and erasing the code change during differentiation. Using a combination of genetic, genomic, biochemical, molecular, and cellular approaches, my current work is aimed at understanding how cells integrate extracellular signals to histone modification writers and erasers, and how these enzymatic changes affect cell fate decision.
1. Lardenois A, Becker E, Walther T, Law MJ, Xie B, Demougin P, Strich R, Primig M. "Global alterations of the transcriptional landscape during yeast growth and development in the absence of Ume6-dependent chromatin modification." Molecular Genetics Genomics. 2015 May 10.
2. Law MJ, Ciccaglione K. "Fine-tuning of histone H3 Lys4 methylation during pseudohyphal differentiation by the CDK submodule of RNA polymerase II." Genetics. 2015 Feb;199(2):435-53. doi: 10.1534/genetics.114.172841. Epub 2014 Dec 1
3. Stuparevic I, Becker E, Law MJ, Primig M. "The histone deacetylase Rpd3/Sin3/Ume6 complex represses an acetate-inducible isoform of VTH2 in fermenting budding yeast cells." FEBS Lett. 2015 Apr 2;589(8):924-32. doi: 10.1016/j.febslet.2015.02.022. Epub 2015 Feb 26.
4. Liu Y, Stuparevic I, Xie B, Becker E, Law MJ, Primig M. "The conserved histone deacetylase Rpd3 and the DNA binding regulator Ume6 repress BOI1's meiotic transcript isoform during vegetative growth in Saccharomyces cerevisiae." Mol Microbiol. 2015 Feb 24
5. Becker E, Liu Y, Lardenois A, Walther T, Horecka J, Stuparevic I, Law MJ, Lavigne R, Evrard B, Demougin P, Riffle M, Strich R, Davis RW, Pineau C, Primig M." Integrated RNA- and protein profiling of fermentation and respiration in diploid budding yeast provides insight into nutrient control of cell growth and development." J Proteomics. 2015 Apr 24;119:30-44. doi: 10.1016/j.jprot.2015.01.015. Epub 2015 Feb 4.
6. Lardenois A, Stuparevic I, Liu Y, Law MJ, Becker E, Smagulova F, Waern K, Guilleux MH, Horecka J, Chu A, Kervarrec C, Strich R, Snyder M, Davis RW, Steinmetz LM, Primig M." The conserved histone deacetylase Rpd3 and its DNA binding subunit Ume6 control dynamic transcript architecture during mitotic growth and meiotic development." Nucleic Acids Res. 2015 Jan;43(1):115-28. doi: 10.1093/nar/gku1185. Epub 2014 Dec 3.
7. Law MJ, Mallory MJ, Dunbrack RL Jr, Strich R." Acetylation of the transcriptional repressor Ume6p allows efficient promoter release and timely induction of the meiotic transient transcription program in yeast." Mol Cell Biol. 2014 Feb;34(4):631-42
8. Law, M.J., Lee D. S., Lee C. S., Anglim P. P., Haworth I. S., and Laird-Offringa, I.A. 2013. "The role of the C-terminal helix in the interaction of U1A protein with U1hpII RNA." Nucleic Acids Res. 2013 Aug 1;41(14):7092-100.
9. Mallory M.J.*, Law, M.J.*, Sterner D.E., Berger S.L., Strich R. 2012." Gcn5p-dependent acetylation induces degradation of the meiotic transcriptional repressor Ume6p." Mol Biol Cell. 23(9):1609-17.
10. Cooper, K.F., Krasley E. Scarnati M.S., Mallory M.J., Jin C., Law M.J., Strich R. 2012." Oxidative stress-induced nuclear to cytoplasmic relocalization is required for Not4-dependent cyclin C destruction." J Cell Sci. 125:1015-26.
11. Mallory, M. J., M. J. Law, and R. Strich. "Sin3p mediates the meiotic transcription program in yeast 2010." Eukaryotic Cell . Vol. 9, No. 12: 1535-9778 (2010 December ) .
12. Law, M.J., Linde, M.E., Chambers, E.J., Oubridge, C., Katsamba, P.S., Nilsson, L., Haworth, I.S., Laird-Offringa, I.A. "The role of positively charged amino acids and electrostatic interactions in the complex of U1A protein and U1 hairpin II RNA." Nucleic Acids Res. Vol. 34: 275-285 (2006 ) .
13. Law, M.J., Rice, A.J., Lin, P., Laird-Offringa, I.A. "The role of RNA structure in the interaction of U1A protein with U1hpII RNA." RNA . Vol. 12: 1-11 (2006 ) .
14. Law, M.J., Chambers, E.J., Katsamba, P.S., Haworth, I.S., Laird-Offringa, I.A. "Kinetic analysis of the role of the tyrosine 13, phenylalanine 56, and glutamine 54 network in the U1A/U1hpII interaction." Nucleic Acids Res. Vol. 33: 2917-2928 (2005 ) .