Steven Jacobsen
email: jacobsen@ucla.edu
phone: (310) 825-0182
fax: (310) 206-3987
office: 3229 Life Sciences
lab: 3218
homepage: http://www.mcdb.ucla.edu/Research/Jacobsen/LabWebSite/index.html
Research Interests
We are interested in cell memory, or the process by which dividing cells inherit states of gene activity. In particular, our work focuses on epigenetic modifications of chromatin including cytosine DNA methylation and histone modifications. We are using Arabidopsis thaliana as a model genetic system to study how these modifications function in gene silencing. Much of our work stems from the discovery of a series of hypermethylated SUPERMAN (SUP) epigenetic alleles in Arabidopsis (Science 277, 1100-1103). These alleles are associated with dense methylation of the promoter and coding regions of the SUP gene and accompanied by a decreased level of SUP RNA. We also find that a number of Arabidopsis mutants which decrease cytosine methylation, surprisingly, give rise to new hypermethylated sup alleles. This is superficially similar to a phenomenon found in many mammalian cancer cells which show overall genomic demethylation coupled with hypermethylation of specific tumor suppressor genes. We are utilizing these epigenetic alleles of SUP, and of a second gene involved in floral development called FWA, to study the genetics of gene silencing. Our mutant screens have recently uncovered the major CpNpG DNA methyltransferase CMT3 (Science, 292:2077-2080), and the major histone H3 Lysine 9 methyltransferase KRYPTONITE (Nature 416: 556-560), involved in gene silencing. We are now cloning other genes in this pathway, and beginning biochemical analysis of the proteins. The other major project in the lab concerns the de novo DNA methyltransferase DRM2. We are using both genetics and biochemistry to work out the mechanisms by which cells initially recognized and silence genes. See lab web site for more details http://www.mcdb.ucla.edu/Research/Jacobsen/index.html
Selected Publications
Jong Kyong Kim, Pierre Esteve, Steven E. Jacobsen and Sriharsa Pradhan. 2009. UHRF1 binds G9a and participates in p21 transcriptional regulation in mammalian cells Nucleic Acids Research 37: 493-505 .
Julie A. Law and Steven E. Jacobsen. 2009. Dynamic DNA methylation Science 323: 1568-1569 .
Nicolas Widman, Steven E. Jacobsen and Matteo Pellegrini. 2009. Determining the conservation of DNA methylation in Arabidopsis Epigenetics 4: 119-124 .
Pierre-Olivier Estève, Hang Gyeong Chin, Jack Benner, George R. Feehery, Mala Samaranayake, Gregory A. Horwitz, Steven E. Jacobsen and Sriharsa Pradhan. 2009. Regulation of DNMT1 stability through SET7-mediated lysine methylation in mammalian cells Proc. Nat. Acad. Sci. U.S.A 106: 5076-5081 .
Xiaoyu Zhang, Yana V Bernatavichute, Shawn Cokus, Matteo Pellegrini and Steven E Jacobsen. 2009. Genome-wide analysis of mono-, di- and trimethylation of histone H3 lysine 4 in Arabidopsis thaliana Genome Biology 10: R62- .
Juliana J. Oh, Baher N. Boctor, Cynthia A. Jimenez, Roberto Lopez, Ashley K. Koegel, Eileen O. Taschereau, Diana T. Phan, Steven E. Jacobsen, Dennis J. Slamon. 2008. Promoter methylation study of the H37/RBM5 tumor suppressor gene from the 3p21.3 human lung cancer tumor suppressor locus Human Genetics 123: 55-64 .
Carey F. Li, Ian R. Henderson, Liang Song, Nina Federoff, Thierry Lagrange, and Steven E. Jacobsen. 2008. Dynamic regulation of ARGONAUTE4 within multiple nuclear bodies in Arabidopsis thaliana PLoS Genetics 4: e27- .
Shawn J. Cokus, Suhua Feng, Xiaoyu Zhang, Zugen Chen, Barry Merriman, Christian D. Haudenschild, Sriharsa Pradhan, Stanley F. Nelson, Matteo Pellegrini & Steven E. Jacobsen. 2008. Shotgun bisulphite sequencing of the Arabidopsis genome reveals DNA methylation patterning Nature 452: 215-219 .
Alan M. Jones, Joanne Chory, Jeffery L. Dangl, Mark Estelle, Steven E. Jacobsen, Elliot M. Meyerowitz, Magnus Nordborg & Detlef Weigel. 2008. The Impact of Arabidopsis on Human Health: Diversifying Our Portfolio Cell 133: 939-943 .
Ian R. Henderson & Steven E. Jacobsen. 2008. Tandem repeats upstream of the Arabidopsis endogene SDC recruit non-CG DNA methylation and initiate siRNA spreading Genes and Development 22: 1597-1606 .