Richard Young, Ph.D.
Department of Biology
Professor of Biology
Member, Whitehead Institute for Biomedical Research
Ph.D. Molecular Biophysics and Biochemistry, 1979
My laboratory has developed powerful genomics methods to map how protein regulators control gene expression programs in healthy and diseased cells. These methods were first used in yeast to discover how gene expression programs are controlled by transcription factors, chromatin regulators, and signaling pathways. Among the key concepts that emerged from these studies is that transcription factors that control cell state typically regulate their own gene expression, that chromatin modifications span active genes in a spatially specific manner, and that signaling pathways have terminal kinases that generally occupy the set of genes they regulate.
These concepts and genome-wide methods have been used recently to map the transcriptional regulatory networks that control pluripotency and self-renewal in human embryonic stem cells, to determine how epigenetic regulators contribute to the embryonic cell state, and to reveal initiation and elongation control mechanisms in mammalian cells. We discovered that ES cell master transcription factors form an interconnected autoregulatory loop and thus feedback regulate their own expression, that Polycomb and SetDB1 chromatin regulators contribute to silencing of genes encoding developmental regulators, and that certain transcription factors regulate transcription initiation while others regulate elongation.
These studies form the foundation for improved understanding of cellular regulation in human health and disease, for efforts to reprogram cells for regenerative medicine and for development of new therapies for cancer.
- 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., Bell, S.P. and Young, R.A. Genome-wide location and function of DNA-binding proteins. Science 290: 2306-2309 (2000).
- Harbison, C.T., Gordon, D.B., Lee, T.I., Rinaldi, N., Macisaac, K.D., Danford, T.D., Hannett, N.M., Tagne, J.-B., Reynolds, D.B., Yoo, J., Jennings, E.G., Zeitlinger, J. Pokholok, D.K., Kellis, M., Rolfe, P.A., Takusagawa, K.T., Lander, E.S., Gifford, D.K., Fraenkel, E. and Young, R.A.Transcriptional Regulatory Code of a Eukaryotic Genome. Nature 431: 99-104 (2004).
- Boyer, L.A., Lee, T.I., Cole, M.F., Johnstone, S.E., Levine, S.S., Zucker, J.P., Guenther, M.G., Kumar, R.M., Murray, H.L., Jenner, R.G., Melton, D.A., Gifford, D.K., Jaenisch, R. and Young, R.A. Core Transcriptional Regulatory Circuitry in Human Embryonic Stem Cells. Cell 122: 947–956 (2005)
- Lee, T.I., Jenner, R.G., Boyer, L.A., Guenther, M.G., Chevalier, B., Levine, S.S., Kumar, R.M., Johnstone, S.E., Murray, H.L., Zucker, J.P., Yuan, B., Bell, G.W., Herbolsheimer, E., Hannett, N.M., Cole, M.F., Sun, K., Odom, D.T., Volkert, T.L., Bartel, D.P., Gifford, D.K., Melton, D.A., Jaenisch, R. and Young, R.A. Control of Developmental Regulators by Polycomb in Human Embryonic Stem Cells. Cell 125: 301-313 (2006).
- Pokholok, D.K., Zeitlinger, J., Hannett, N., Reynolds, D., and Young, R.A. Activated Signal Transduction Kinases Frequently Occupy Target Genes. Science 313: 533-536 (2006).
- Guenther, M., Levine, S.S., Boyer, L.A., Jaenisch, R. and Young, R.A. A Chromatin Landmark and Transcription Initiation at Most Promoters in Human Cells. Cell 130, 77-88 (2007).
- Jaenisch, R. and Young, R.A. Stem Cells, the Molecular Circuitry of Pluripotency and Nuclear Reprogramming. Cell 132: 567–582 (2008).
- Marson, A. , Levine, S.S., Cole, M.F., Frampton, G.M., Brambrink, T., Johnstone, S., Guenther, M.G., Johnston, W.K., Wernig, M., Newman, J., Calabrese, J.M., Dennis, L.M., Volkert, T.L., Gupta, S., Love, J., Hannett, N., Sharp, P.A., Bartel, D.P., Jaenisch, R., and Young, R.A. Connecting microRNA genes to the core transcriptional regulatory circuitry of embryonic stem cells. Cell 134:521-533 (2008).
- Kagey, M.H., Newman, J.J, Bilodeau, S., Zhan, Y., van Berkum, N.L., Orlando, D.A., Ebmeier, C.C., Goossens, J., Rahl, P., Levine, S., Taatjes, D.J., Dekker, J. and Young, R.A. Mediator and cohesin connect gene expression and chromatin architecture. Nature 467: 430-435 (2010).
- Rahl, P.B., Lin, C.Y., Seila, A.C., Flynn, R.A., McCuine, S., Burge, C.B., Sharp, P.A., and Young, R.A. c-Myc regulates transcriptional pause release. Cell 141, 432–445 (2010).
Last Updated: January 20, 2011