Itamar Simon

Department of Molecular Biology,

Tel. 972-2-6758544

Fax. 972-2-678992

E-mail. itamars@md.huji.ac.il

Laboratory members

Zahava Siegfried, Ph.D.

Shlomit Farkash

Helena Medvedovsky

Ran Rubinstein

Idit Shiff

Adam Strier

Research

The development of an organism requires the differential transcription of many genes in precise spatial and temporal patterns. This is gained by a limited number of transcription factors, most probably due to the fact that each factor can participate in multiple processes. The differential regulation of various sets of genes by a common transcription factor can be achieved by few mechanisms including: 1. Combinatorial regulation – the specific control is done by combination of factors and not by a single one. 2. Protein modifications – different forms of a transcription factor activates different sets of genes. 3. Promoter structure – variation in the DNA binding site and modification in the chromatin structure, can affect the binding of the transcription factor to different promoters.

We are trying to employ genomics tools (such as expression profiles with high density DNA microarrays and a genomic version of chromatin immuno precilitation) in addition to conventional molecular biology tools, for elucidating such questions. Currently we are working on the following projects:

   I.       Transcription regulation of the yeast cell cycle.

II.     P53 involvement in apoptosis and cell cycle arrest.

III.    The involvement of beta catenin in colon cancer and melanoma.

IV.  Genome-wide hypermethylation of CpG islands during cancer transformation.

Relevant publications

Ren, B., Robert, F., Wyrick, J. J., Aparicio, O., Jennings, E. G., Simon, I., Zeitlinger, J., Schreiber, J., Hannett, N., Kanin, E., Volkert, T. L., Wilson, C. J., Bell, S. P., and Young, R. A. (2000). Genome-wide location and function of DNA binding proteins. Science 290, 2306-2309.

Simon, I., Barnett, J., Hannett, N., Harbison, C., Rinaldi, N., Volkert, T., Wyrick, J., Zeitlinger, J., Gifford D. K.,  Jaakkola T. S. and Young, R. A. (2001). Serial regulation of transcriptional regulators in the yeast cell cycle. Cell 106, 697-708.

Damelin M., Simon I., Moy T. I., Wilson B., Komili S., Tempst P., Roth F. P., Young R. A., Cairns B. R., and Silver P. A. (2001). The Genome-Wide Localization of Rsc9, a Component of the RSC Chromatin-Remodeling Complex, Changes in Response to Stress. Molecular Cell 9, 563-573.

Segal, E., Barash, Y., Simon, I., Friedman, N. and Koller, D.(2002). From promoter sequence to expression: a probabilistic framework.  In Proc. Fifth Annual International Conference on Computational Molecular Biology (RECOMB) G.Myers et al.,Eds.(ACM Press, New York, 2002). 263-272.

Lee, T. A., Rinaldi, N. J., Robert, F.,  Odom, D. T., Bar-Joseph, Z., Gerber. G. K., Hannett, N. M., Harbison, C. T., Thompson, C. M., Simon, I., Zeitlinger, J., Jennings, E. G., Murray, H. L., Gordon, D.B., Ren, B., Wyrick, J. J., Tagne, J-B., Volkert, T. L., Fraenkel, E., Gifford, D. K. and Young, R. A. (2002). Transcriptional Regulatory Networks in Saccharomyces cerevisiae. Science 298, 799-804.

Zeitlinger, J., Simon, I., Harbison, C. T., Hannett, N. M., Volkert, T. L., Fink, G. R. and Young, R. A. (2003).  Program-Specific Distribution of a Transcription Factor Dependent on Partner Transcription Factor and MAPK Signaling. Cell 113, 395–404.

Shen W-C., Bhaumik S.R.,  Causton H.C., Simon, I., Zhu, X., Jennings, E.G., Wang, T-H., Young, R.A. and Greem M.R. (2003). Systematic Analysis of Essential Yeast TAFs in Genome-Wide Transcription and Pre-Initiation Complex Assembly. EMBO, 22, 3395-3402.

Bar-Joseph, Z., Gerber, G., Simon, I., Gifford, D.K. and Jaakkola, T.S. (2003). Comparing the Continuous Representation of Time Series Expression Profiles to Identify Differentially Expressed Genes. PNAS, 100, 10146-10151. 

Bar-Joseph Z, Gerber GK, Gifford DK, Jaakkola TS, Simon I (2003). Continuous representations of time-series gene expression data. J Comput Biol., 10, 341-356.

Bar-Joseph Z, Farkash S, Gifford DK, Simon I, Rosenfeld R (2004). Deconvolving cell cycle expression data with complementary information. Bioinformatics, 20 Suppl 1:I23-I30.

Rubinstein R. and Simon I. (2005). MILANO – custom annotation of microarray results using automatic literature searches. BMC Bioinformatics, 6, 12- 20.

Simon I., Siegfried Z., Ernst J. and Bar-Joseph Z. (2005) Combining Static and Time Series Data to Determine the Quality of Expression Profiles in Time Series Experiments. Nature Biotechnology, 23, 1503-1508.

Keshet I., Schlesinger Y.,  Farkash S., Rand E.,  Hecht M., Segal E., Pikarski E., Young RA.,  Niveleau A., Cedar H. and Simon I. (2006) Pathways of de novo methylation in cancer cells. Nature Genetics, 38, 149-153.