Yi Zhang, PhD

• Zhang Lab Website
• Publication List

RESEARCH INTERESTS:

Epigenetic Modifications and Their Role in Cellular Memory and Cancer

Epigenetic modifications, particularly DNA methylation and covalent histone modifications, play an important role in regulating chromatin dynamics and therefore have a significant impact on gene expression. Our lab is interested in how epigenetic-mediated dynamic changes in chromatin structure affect gene expression, cell lineage commitment and cancer development. Our long-term goal is to apply this basic research to studies of human diseases.

Studies in our lab focus on four different areas:

I. The relationship between ATP-dependent nucleosome remodeling and histone deacetylation. This area of study focuses on the nucleosome remodeling and deacetylase complex NuRD which we have recently demonstrated also plays an important role in methylated DNA silencing. We use a combination of biochemical and mouse genetic approaches to understand its biological function and the underlying mechanism through identification of its target genes by a genome wide localization approach. Our recent studies have linked its function to the autoimmune disease Lupus.

II. The identification and characterization of novel covalent histone modifiers. Thus far, we have identified several novel histone methyltransferases including PRMT1, SET7, SET8, ESET, EZH2, and hDOT1. Our preliminary studies suggest that several of the enzymes are potentially involved in cancer. For example, the EZH2 protein has been linked to several types of solid cancers and hDOT1 has been linked to leukema. We have also recently identified several histone demethylases by using a novel biochemical assay. We are currently working to characterize these proteins.

III. The role of various epigenetic modifications in cell lineage commitment, maintenance, and stem cell biology. Our goal is to identify a cell lineage or stem cell specific histone modification patterns and then to address the role of these histone modifications in the cell lineage commitment and maintenance process. 

IV. The identification and characterization of small chemical compounds that can modulate the enzymatic activities that have been mentioned above. By performing high-throughput screening followed by in vitro and in vivo verification, we hope to identify leading compounds for drug development. 

For more information, please visit our web page at http://www.med.unc.edu/~zhangyi/lab.htm.

REPCENT PUBLICATIONS:

Kotake, Y., Cao, R., Viatour, P., Sage, J., Zhang, Y., & Xiong, Y. pRB family proteins are required for H3K27 trimethylation and Polycomb repression complexes binding to and silencing p16 INK4a tumor suppressor gene. Genes & Development. 21: 49-54. 2007

Liang, G., Klose, R.J., Gardner, K.E., & Zhang, Y. Yeast Jhd2p is a histone H3 Lys4 trimethyl demethylase. Nat. Struct. & Mol. Bio. 14:243-245. 2007

Klose, R.J., Yan, Q., Tothova, Z., Yamane, K., Erdjument-Bromage, H., Tempst, P., Gilliland, D.G., Zhang, Y., & Kaelin, W.G. The Retinoblastoma Binding Protein RBP2 is an H3K4 demethylase. Cell. 128:889-900. 2007

Lee, N., Zhang, J., Klose, R.J., Erdjument-Bromage, H., Tempst, P., Jones, R.S., & Zhang, Y. The trithorax-group protein Lid is a histone H3 trimethyl-Lys4 demethylase. Nat. Struct. & Mol. Bio. 14(4): 341-3. 2007

Klose, R.J., & Zhang, Y. Regulation of histone methylation by demethylimination and demethylation. Nat. Rev. M.C.B. 8(4): 307-18. 2007

Yamane, K., Tateishi, K., Klose, R.J., Fang, J., Fabrizio, L.A., Erdjument-Bromage, H., Taylor-Papadimitriou, J., Tempst, P., & Zhang, Y. PLU-1 is an H3K4 demethylase involved in transcriptional repression and breast cancer cell proliferation. Mol.Cell. 25(6): 801-12. 2007

Martin, C., & Yi Zhang. Mechanisms of epigenetic inheritance. Curr. Opin. Cell Bio. 19:266-72. 2007

Klose, R.J., Gardner, K.E., Liang, G., Erdjument-Bromage, H., Tempst, P., & Zhang, Y. Demethylation of histone H3K36 and H3K9 by Rph1: a zestige of an H3K9 methylation system in Saccharomyces cerevisiae? MCB. 27:3951-3961. 2007

Fang, J., Hogan, G.J., Liang, G., Lieb, J.D., & Zhang, Y. The Saccharomyces cerevisiae histone demethylase Jhd1 fine-tunes the distribution of H3K36me2. MCB. 27:5055-65. 2007

Okada, Y., Scott, G., Ray, M.K., Mishina, Y., & Zhang, Y. Histone demethylase JHDM2A is critical for Tnp1 and Prm1 transcription and spermatogenesis. Nature. 450:119-123. 2007

Klose, R.J. & Zhang Y. Histone H3 Arg2 methylation provides alternative directions for COMPASS. Nat.Struct.Mol.Biol. 14(11):1058-60. 2007

Allis, C.D., Berger, S.L., Cote, J., Dent, S., Jenuwien, T., Kouzarides, T., Pillus, L., Reinberg, D., Shi, Y., Shiekhattar, R., Shilatifard, A., Workman, J., Zhang, Y. New nomenclature for chromatin modifying enzymes. Cell. 131(4):633-6. 2007

Feldman, N., Gerson, A., Fang, J., Li, E., Zhang, Y., Shinkai, Y., Cedar, H., & Bergman, Y. G9a-mediated irreversible epigenetic inactivation of Oct-3/4 during early embryogenesis. Nature Cell Biology. 8: 188-194. 2006

Kim, J., Daniel, J., Espejo, A., Lake, A., Krishna, M., Xia, L., Zhang, Y., & Bedford, M.T. Tudor, MBT and chromo domains gauge the degree of lysine methylation. EMBO Reports. 7:397-403. 2006

Martin, C., Cao, R., & Zhang,Y. Substrate preferences of the EZH2 histone methyltransferase complex. JBC. 281:8365-70. 2006

Tsukada, Y., Fang, J., Erdjument-Bromage, H., Warren, M.E., Borchers, C.H., Tempst, P., & Zhang,Y. Histone demethylation be a family of JmjC domain-containing proteins. Nature. 439:811-816. 2006

Huang, Y., Fang, J., Bedford, M.T., Zhang, Y., & Xu, R-M. Recognition of Histone H3 Lysine -4 Methylation by the Double Tudor Domain of JMJD2A. Science. 312(5774):748-51. 2006

Yamane, K., Toumazou, C., Tsukada, Y., Erdjument-Bromage, H., Tempst, P., Wong, J., & Zhang, Y. JHDM2A, a JmjC-Containing H3K9 Demethylase, Facilitates Transcription Activation by Androgen Receptor. Cell. 125(3):483-95. 2006

Wang, H., Zhai, L., Xu, J., Joo, H-Y., Jackson, S., Erdjument-Bromage, H., Tempst, P., Xiong, Y., & Zhang, Y. Histone H3 and H4 Ubiquitylation by the CUL4-DDB-ROC1 Ubiquitin Ligase Facilitates Cellular Response to DNA Damage. Mol. Cell. 22(3):383-94. 2006

Klose, R.J., Yamane, K., Bae, Y., Zhang D., Erdjument-Bromage, H., Tempst, P., Wong, J., & Zhang, Y. The transcriptional repressor JHDM3A demethylates trimethyl histone H3 lysine 9 and lysine 36. Nature. 442:312-316. 2006

Li, Z., Cao, R., Wang, M., Myers, M.P., Zhang, Y., & Xu, R-M. Structure of a BMI-1-RING1B polycomb group ubiquitin ligase complex. J.B.C. 281(29):20643-20649. 2006

Zhang, Y. It takes a PHD to interpret histone methylation. Nat. Structural & Mol. Bio. 13(7):572-574. 2006

Klose, RJ., Kallin, EM., & Zhang Y. JmjC-domain-containing proteins and histone demethylation. Nat.Rev.Genetics. 7:715-727. 2006