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Return to: College of Biological Sciences: Medical School: U of M Home |
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Areas of Research Strength: Control of gene expression Chromatin structure and function Animal development back to top |
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Research Techniques: Chromatin modification Chromosome spreads and immunostaining Genetics and developmental biology of Drosophila Biochemistry of protein-protein interactions and nuclear protein complexes back to top |
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Research Interests: Work in the Simon laboratory concerns the molecular mechanisms that control animal development. In order for a multicellular organism to develop properly, specific genes must be turned on or off in specific cells. The lab is studying a set of genes, called homeotic or HOX genes, that control development in the fruit fly, Drosophila. The lab uses a combination of molecular biology, biochemistry, and genetics to study how these genes are regulated in fly embryos. A major project concerns how transcription of HOX genes is repressed in specific body regions. At least 10 proteins, termed Polycomb group (PcG) proteins, have been identified that cooperate to provide repression. These proteins are generally thought to regulate transcription by modifying the chromatin organization of target genes. The lab is studying the molecular mechanisms of protein complexes formed by these repressors. One of these repressor complexes, the ESC-E(Z) complex, has an enzyme activity that methylates a specific lysine residue of histone H3, a fundamental component of eukaryotic chromatin. The lab is seeking to understand how this repressor complex works and how this covalent chromatin modification influences gene expression during development. Mice and humans have HOX genes and Polycomb group repressors that resemble their fly counterparts in structure and function. Furthermore, mammalian versions of PcG repressors, including the E(Z) histone methyltransferase, have been implicated in X-chromosome inactivation and in cancers of the prostate and immune systems. By studying PcG repressors in flies, we expect to gain insight into developmental controls and chromatin mechanisms in higher organisms as well. back to top |
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Selected Publications: Wang, L., Jahren, N., Vargas, M.L., Andersen, E.F., Benes, J., Zhang, J., Miller, E.L., Jones, R.S. and Simon, J.A. (2006). Alternative ESC and ESC-Like subunits of a Polycomb group histone methyltransferase complex are differentially deployed during Drosophila development. Mol. Cell. Biol. 26, 2637-2647. Ketel, C.S., Andersen, E.F., Vargas, M.L., Suh, J., Strome, S. and Simon, J.A. (2005). Subunit contributions to histone methyltransferase activities of fly and worm Polycomb group complexes. Mol. Cell. Biol. 25, 6857-6868. Peterson, A.J., Mallin, D.R., Francis, N.J., Ketel, C.S., Stamm, J., Voeller, R.K., Kingston, R.E. and Simon, J. A. (2004). Requirement for Sex Comb on Midleg protein interactions in Drosophila Polycomb group repression. Genetics 167, 1225-1239. Simon, J.A. (2003). Polycomb group proteins – Quick Guide. Curr. Biol. 13, R79-80. Muller, J., Hart, C.M., Francis, N.J., Vargas, M.L., Sengupta, A., Wild, B., Miller, E.L., O'Connor, M.B., Kingston, R.E. and Simon, J.A. (2002). Histone methyltransferase activity of a Drosophila Polycomb group repressor complex. Cell 111, 197-208 Simon, J.A. and Tamkun, J.W. (2002). Programming off and on states in chromatin: mechanisms of Polycomb and trithorax group complexes. Curr. Opin. Genet. Dev. 12: 210-218. Fang, J., Feng, Q., Ketel, C.S., Wang, H., Cao, R., Xia, L., Erdjument-Bromage, H., Tempst, P., Simon, J.A. and Zhang, Y. (2002). Purification and functional characterization of SET8, a nucleosomal histone H4-lysine 20-specific methyltransferase. Curr. Biol. 12: 1086-1099. Roseman, R., Morgan, K., Mallin, D., Roberson, R., Parnell, T.J., Bornemann, D.J., Simon, J.A. and Geyer, P.K. (2001). Long-range repression by multiple Polycomb group proteins targeted in vivo by fusion to a defined DNA-binding domain. Genetics 158, 291-307. Ng, J., Hart, C.M., Morgan, K. and Simon, J. A. (2000). A Drosophila ESC-E(Z) protein complex is distinct from other Polycomb group complexes and contains covalently modified ESC. Mol. Cell. Biol. 20, 3069-3078. Shimell, M.J., Peterson, A.J., Burr, J., Simon, J. and O'Connor, M. (2000). Functional analysis of repressor binding sites in the iab-2 regulatory region of the abdominal-A homeotic gene. Dev. Biol. 218, 38-52. Tomotsune, D., Takihara, Y., Berger, J., Duhl, D., Joo, S., Kyba, M., Shirai, M., Ohta, H., Matsuda, Y., Honda, B., Simon, J., Shimada, K., Brock, H.W. and Randazzo, F. (1999). A novel member of murine Polycomb-group proteins, Sex comb on midleg homolog protein, is highly conserved and interacts with RAE28/mph1 in vitro. Differentiation 65, 229-239. Bornemann, D., Miller, E. and Simon, J. (1998). Expression and properties of wild-type and mutant forms of the Drosophila Sex Comb on Midleg (SCM) repressor protein. Genetics 150, 675-686. Jones, C.A., Ng, J., Peterson, A.J., Morgan, K., Simon, J. and Jones, R.S. (1998). The Drosophila esc and E(z) proteins are direct partners in Polycomb-group-mediated repression. Mol. Cell. Biol. 18, 2825-2834. To view these and other publications visit http://www.ncbi.nlm.nih.gov/PubMed search menu should say PubMed type Simon JA in the avaliable line back to top |
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