Joanna Wysocka, Ph.D. (Assistant Professor)

Departmental Affiliation:
Chemical and Systems Biology, Developmental Biology.

Graduate Program(s):
Chemical and Systems Biology, Developmental Biology

Email:wysocka@stanford.edu


Keywords: histone modifications, chromatin, epigenetics,embryonic stem cells, vertebrate development

Research description:

The biological question that is driving our research in the long-term is understanding the epigenetic basis of vertebrate development and differentiation, and how its misregulation may lead to the oncogenic transformation. Development is an epigenetically regulated process, in which gene expression patterns are established and maintained throughout cell divisions. Over the recent years it has become clear that establishment and propagation of gene expression patterns involve proteins which modify chromatin structure through covalent modification of histones and associated DNA, and ATP-dependent chromatin remodeling.

            Our research focuses on understanding the mechanistic basis by which covalent histone modifications regulate gene expression patterns during vertebrate development and differentiation. In particular, we are focusing on characterizing enzymatic activities responsible for "writing" the methyl mark on histones, called histone methyltransferases, as well as on downstream effectors, or "readers", which recognize the methyl marks and translate them into specific biological outcomes.

            A second major area of our interest involves chromatin regulation in embryonic stem cells and molecular basis of pluripotency. Our goal is to link the transcription factors that specify embryonic stem cell identity with chromatin modifying machinery that is essential for mediating this specification, and to identify major players in recognizing modified histone tails in human and mouse embryonic stem cells.

Representative publications:

Wysocka J., Swigut T., Xiao H., Landry J., Kauer M., Tackett A.J., Chait B.T., Wu C. and Allis C.D. 2006. A PHD finger of the largest NURF subunit couples histone H3 K4 trimethylation with chromatin remodeling. Nature 442:86-90

Li H.-T., Ilin-Schneider S., Wang W.-K., Wysocka J., David Allis C.D. and Patel D.J. 2006. Molecular basis for site/state-specific readout of histone lysine-methylation marks by the PHD domain of BPTF. Nature 442:91-5

Wysocka J., Milne T.A. and Allis C.D. 2005. Taking LSD1 to a New High. Cell 122(5):654-658

Wysocka J., Swigut T., Milne T.A., Dou Y., Zhang X., Burlingame A.L., Roeder R.G., Brivanlou A.H. and Allis C.D. 2005. WDR5 associates with histone H3 methylated at K4 and is essential for H3 K4 methylation and vertebrate development. Cell, 121(6):859-872.

Dou Y., Milne T.A., Tackett A.J., Smith E.R., Fukuda A., Wysocka J., Allis C.D., Chait B.T., Hess J.L. and Roeder R.G. 2005. Physical association and coordinate function of the H3 K4 methyltransferase MLL1 and the H4 K16 acetyltransferase MOF. Cell, 121(6):873-885.

Wang Y., Wysocka J., Sayegh J., Lee Y.H., Perlin J.R., Leonelli L., Sonbuchner L.S., McDonald C.H., Cook R.G., Dou Y., Roeder R.G., Clarke S., Stallcup M.R., Allis C.D. and Coonrod S.A. 2004. Human PAD4 regulates histone arginine methylation levels via demethylimination. Science , 306(5694):279-283.

Wysocka J., Myers M.P., Laherty C.D., Eisenman R.N. and Herr W. 2003. Human Sin3 deacetylase and trithorax-related Set1/Ash2 histone H3 lysine 4 methyltransferase are tethered together selectively by the cell-proliferation factor HCF-1. Genes and Development 17: 896-911.