Jia Fang, PhD

The research in my laboratory is focused on the molecular mechanisms of various histone modifications regulate the chromatin structure and in turn mediate different cellular processes. Particular emphasis is devoted to identify and characterize novel histone-modifying enzymes and regulatory proteins which mediate downstream effects and chromatin organization. The long term goal of this research is to understand the role of these epigenetic modifications in various diseases, particularly in human cancer. Using an activity-based biochemical approach,

I have identified and characterized several histone-modifying enzymes including SET domain-containing histone H4K20 methyltransferase SET8 and Jmjc domain-containing histone H3K36 demethylase JHDM1. I have also demonstrated that different polycomb group protein complexes PRC1 and PRC2, and their mediated histone H2A-K119 ubiquitination and histone H3-K27 methylation play important roles in X chromosome inactivation. 

Ongoing studies are to further dissect the molecular mechanism of histone H4-K20 methylation, demethylation and their potential roles in tumorigenesis. The lab is also interested in elucidating the role of histone modifications in various processes including transcriptional regulation, heterochromatin formation and X chromosome inactivation.

• Zheng H, Chen L, Pledger WJ, Fang J, Chen J. p53 promotes repair of heterochromatin DNA by regulating JMJD2b and SUV39H1 expression. Oncogene. 2013 Feb. Pubmedid: 23376847.
• Sun L, Fang J. Writer meets eraser in HOTAIR. Acta Biochim Biophys Sin (Shanghai). 2011 Jan;43(1):1-3. Pubmedid: 21138898.
• Chang Y, Sun L, Kokura K, Horton JR, Fukuda M, Espejo A, Izumi V, Koomen JM, Bedford MT, Zhang X, Shinkai Y, Fang J, Cheng X. MPP8 mediates the interactions between DNA methyltransferase Dnmt3a and H3K9 methyltransferase GLP/G9a. Nat Commun. 2011;2:533. Pubmedid: 22086334. Pmcid: PMC3286832.
• Kokura K, Sun L, Bedford MT, Fang J. Methyl-H3K9-binding protein MPP8 mediates E-cadherin gene silencing and promotes tumour cell motility and invasion. EMBO J. 2010 Nov;29(21):3673-3687. Pubmedid: 20871592. Pmcid: PMC2982762.
• Li Z, Chen L, Kabra N, Wang C, Fang J, Chen J. Inhibition of SUV39H1 methyltransferase activity by DBC1. J Biol Chem. 2009 Apr;284(16):10361-10366. Pubmedid: 19218236. Pmcid: PMC2667723.
• Kokura K, Fang J. In vitro histone demethylase assays. Methods Mol Biol. 2009;523:249-261. Pubmedid: 19381934.
• Fang J, Hogan GJ, Liang G, Lieb JD, Zhang Y. The Saccharomyces cerevisiae histone demethylase Jhd1 fine-tunes the distribution of H3K36me2. Mol Cell Biol. 2007 Jul;27(13):5055-5065. Pubmedid: 17470555. Pmcid: PMC1951470.
• Yamane K, Tateishi K, Klose RJ, Fang J, Fabrizio LA, 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. 2007 Mar;25(6):801-812. Pubmedid: 17363312.
• Huang Y, Fang J, Bedford MT, Zhang Y, Xu RM. Recognition of histone H3 lysine-4 methylation by the double tudor domain of JMJD2A. Science. 2006 May;312(5774):748-751. Pubmedid: 16601153.
• Tsukada Y, Fang J, Erdjument-Bromage H, Warren ME, Borchers CH, Tempst P, Zhang Y. Histone demethylation by a family of JmjC domain-containing proteins. Nature. 2006 Feb;439(7078):811-816. Pubmedid: 16362057.
• 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. Nat Cell Biol. 2006 Feb;8(2):188-194. Pubmedid: 16415856.
• de la Cruz CC, Fang J, Plath K, Worringer KA, Nusinow DA, Zhang Y, Panning B. Developmental regulation of Suz 12 localization. Chromosoma. 2005 Aug;114(3):183-192. Pubmedid: 15986205.
• Fang J, Chen T, Chadwick B, Li E, Zhang Y. Ring1b-mediated H2A ubiquitination associates with inactive X chromosomes and is involved in initiation of X inactivation. J Biol Chem. 2004 Dec;279(51):52812-52815. Pubmedid: 15509584.
• Plath K, Fang J, Mlynarczyk-Evans SK, Cao R, Worringer KA, Wang H, de la Cruz CC, Otte AP, Panning B, Zhang Y. Role of histone H3 lysine 27 methylation in X inactivation. Science. 2003 Apr;300(5616):131-135. Pubmedid: 12649488.
• Fang J, Feng Q, Ketel CS, Wang H, Cao R, Xia L, Erdjument-Bromage H, Tempst P, Simon JA, Zhang Y. Purification and functional characterization of SET8, a nucleosomal histone H4-lysine 20-specific methyltransferase. Curr Biol. 2002 Jul;12(13):1086-1099. Pubmedid: 12121615.
• Fang J, Wang H, Zhang Y. Purification of histone methyltransferases from HeLa cells. Methods Enzymol. 2004 377;377:213-226. Pubmedid: 14979027.