Andrew K. Vershon
Professor

Transcriptional regulation in yeast

Our research focuses on the transcriptional regulation of genes in the yeast Saccharomyces cerevisiae. Specifically. we are investigating how different regulatory proteins interact to control gene expression and how these interactions influence the regulatory activity of these proteins. Many of the factors that we are studying in yeast are closely related in structure and function to regulatory proteins in higher eukaryotes that play critical roles in processes such as development and cancer. Investigations into the activity and role of these transcription factors in yeast therefore provides valuable information on the function of the homologous proteins in multi-cellular organisms.

We have chosen three different regulatory systems to study the mechanisms that control gene expression: 1) examining the protein-protein and protein-DNA interactions of the Mat2 protein. a member of the highly conserved homeodomain family of DNA- binding proteins. which functions as a cell-type specific repressor involved in mating-type regulation. 2) examining the molecular interactions of the Mcm1 protein. a MADS-Box protein that is involved in the transcriptional regulation of cell-type and metabolic pathways and has an essential role in the regulation of genes expressed at specific stages of the cell cycle. and 3) investigating the mechanism of temporal regulation of genes expressed at the middle stages of meiosis. including the analysis of proteins involved in histone modification and the characterization of novel DNA-binding proteins with human homologs that are associated with cancer. Our laboratory utilizes a combination of biochemical. genetic. structural and bioinformatics techniques. including microarray gene expression analysis and screens of the yeast genome deletion library. to investigate the mechanism of transcriptional regulation in yeast.

Selected Publications

Mead J, McCord R, Youngster L, Sharma M, Gartenberg MR, Vershon AK. (2007) Swapping the gene-specific and regional silencing specificities of the Hst1 and Sir2 histone deacetylases. Mol Cell Biol. 27(7):2466-75.

Abraham DS. Vershon AK. (2005) N-terminal arm of Mcm1 is required for transcription of a subset of genes involved in maintenance of the cell wall. Eukaryot Cell. 4(11):1808-19.

Hanlon. S.E.. Xu. Z.. Norris. D.N.. and Vershon. A. K. (2004) Analysis of the meiotic role of the mitochondrial ribosomal proteins Mrps17 and Mrpl37. Yeast 21:1241-1252.

Nagaraj. V.H.. Flanagan. R.O.. Bruning. A.R.. Mathias. J.R. Vershon. A. K.. and Sengupta. A. M. (2004) Identification of a1-a2 binding sites in the yeast genome. BMC Genomics 5:59.

Mathias. J.R. Hanlon. S.E.. Flanagan. R.O.. Sengupta. A. M. and Vershon. A.K. (2004) Repression of the yeast HO gene by the MATa2 and MATa1 homeodomain proteins. Nucleic Acid Res. 32:6469-6478.

Carr. E. A.. Mead. J. and Vershon. A. K. (2004) a1-induced DNA bending is required for transcriptional activation by the Mcm1-a1 complex. Nucleic Acid Res. 32:2298-2305.

Fingerman. I.. Sutphen. K.. Montano. S. P.. Georgiadis. M.M.. and Vershon. A. K. (2004) The yeast Ndt80 protein binds DNA through a series of flexible loops. Nucleic Acid Res. 32: 2947-2956.

Fingerman. I. . Nagaraj. N.. Norris. D.N. and Vershon. A.K. (2003). The yeast Sfp1 protein plays a key role in ribosome biogenesis. Euk. Cell 2:1061-1068.

Hanlon. S.E. Norris. D.N. and Vershon. A. K. (2003) Depletion of H2A-H2B dimers in Saccharomyces cerevisiae triggers meiotic arrest by reducing IME1 expression and activating the BUB2-dependent branch of the spindle checkpoint. Genetics 164:1333-1344.

Pierce. M.. Benjamin. K.R.. Montano. S. P.. Georgiadis. M.M.. Winter. E.. and Vershon. A. K. (2003) Sum1 and Ndt80 Proteins Compete for Binding to MSE Sequences that Control Meiotic Gene Expression. Mol. Cell. Biol. 23:4814-4825.

McCord. R.. Pierce. M.. Xie. J.. Wonkatal. S.. Mickel. C. and Vershon. A.K. (2003) Rfm1. a novel factor required to recruit the Hst1 histone deacetylase for repression of middle sporulation genes. Mol. Cell. Biol. 23:2009-2016.

Montano. S.P.. Cote. M.. Pierce. M.. Vershon. A. K. Georgiadis. M. M. (2002). Crystallographic studies of a novel DNA-binding domain from the yeast transcriptional activator Ndt80. Acta. Crys.D. 58:2127:2130.

Montano. S.P.. Cote. M.. Fingerman. I.. Pierce. M.. Vershon. A. K. Georgiadis. M. M. (2002). The crystal structure of a novel DNA-binding domain from Ndt80. a transcriptional activator required for meiosis in yeast. Proc. Natl. Acad. Sci. 99:14041-14046.

Jamai. A.. Dubois. E. Vershon. A.K.. and Messenguy. F. (2002). Swapping functional specificity of a MADS-box protein: Residues required for Arg80 regulation of arginine metabolism. Mol. Cell. Biol. 22:5741-5752.

Mead. J.. Bruning. A.. Gill. M.K.. Steiner. A.M.. Acton . T.B. and Vershon. A.K. (2002). Interactions of the Mcm1 MADS-box protein with cofactors that regulate mating in yeast. Mol. Cell. Biol. 22:4607-4621.

Ke. A.. Mathias. J. R.. Vershon. A. K. and C. Wolberger (2002). Structural and thermodynamic characterization of the DNA binding properties of a triple alanine mutant of MATa2. Structure 10:961-971.

Hart. B.. Mathias. J.. Ott. D. McNaughton. L.. Anderson . J.. Vershon. A.K.. and Baxter. S. M. (2002). Engineered improvements in DNA-binding function of the MATa1 homeodomain reveal structural changes involved in combinatorial control. J. Mol. Biol. 316:247-256.

Mathias. J.R.. Zhong. H.. Jin. Y. and Vershon. A.K (2001). Altering the DNA-binding specificity of the yeast Mat2 Homeodomain Protein. J. Biol. Chem. 276:32696-703.

Lindgren. A.. Bungard. D.. Pierce. M.. Xie. J. Vershon. A.K. . and Winter. E. (2000). The pachytene checkpoint in Saccharomyces cerevisiae requires the Sum1 transcriptional repressor. EMBO J 19:6489-97.

Kim. J.. Bortz. E. Zhong. H.. Leeuw T.. Leberer. E. Vershon. A.K. and Hirsch. J.P. (2000). Localization and signaling of G subunit Ste4p are controlled by the a-factor receptor and the novel a-specific protein Asg7p Mol. Cell. Biol. 20:8826-8835.

Vershon. A.K. and Pierce. M. (2000). Transcriptional regulation of meiosis in yeast. Curr. Op. Cell Biol. 12. 334-339.

Acton . T.B.. Mead. J.. Steiner. A.M.. and Vershon. A.K. (2000). Scanning mutagenesis of Mcm1: Residues required for DNA binding. bending and transcriptional activation by a MADS box. Mol. Cell. Biol. 20:1-11.