Title: Epigenetic Anti-silencing and Active DNA Demethylation in Arabidopsis

Presenter: Dr. Cheng-Guo Duan

University: Department of Horticulture and Landscape Architecture, Purdue University, Indiana, USA

Time: 9:00-11:00, December 11, 2015

Venue: Room E301, Institute of Microbiology, Chinese Academy of Sciences

Abstract:

    DNA methylation is critical for genome stability, development and stress responses in plants and mammals. Human aging, and cancers and many other diseases are associated with DNA methylation changes. The status of DNA methylation is determined by the dynamic balance of methylation and demethylation reactions. DNA methylation by methyltransferase enzymes and the interplay between DNA methylation, small interfering RNAs (siRNAs), and histone modification patterns have been studied extensively. In contrast, the mechanism of active DNA demethylation and its regulation are less well understood.

    We used powerful forward genetics screen to discover cellular anti-silencing factors and regulators of DNA demethylation. Our work discovered several new players required for the regulation of DNA demethylation and prevention of transcriptional gene silencing in Arabidopsis. These regulators include ASI1 (anti-silenicng 1), MET18, HDP1 (Harbinger transposon-derived protein 1) and HDP2. ASI1 is required for the proper expression of intronic heterochromatin-containing gene and prevention of gene body CHG hypermethylation. MET18 is the first regulator of ROS1 catalytic activity which connects the Cytosolic Iron-Sulfur cluster Assembly (CIA) pathway to active DNA demethylation. HDP1/HDP2 are derived from same Harbinger transposon ancestor and form a functional module via direct interaction to serve as protein platform for recruiting DNA demethylation machinery. HDP1/HDP2 is the first protein complex that regulates active DNA demethylation and prevents transcriptional gene silencing. Collectively, our work revealed new cellular factors required for active DNA methylation and anti-silencing and threw new insights into the molecular mechanism of DNA demethylation.

Professional and Education Experience

2011.10-present: Postdoctoral Research Assistant, Purdue University

2008.07-2011.10: Assistant Professor, Institute of Microbiology, CAS

2004.09-2008.07: Ph.D degree, Institute of Microbiology, CAS

Key Publications:

First/Co-first author:

[1]. Duan, C.G.#, Wang, X.#, Tang, K., Zhang, H., Mangrauthia, S.K., Lei, M., Hsu, C.C., Hou, Y.J., Wang, C., Li, Y., TAO W.A. Zhu J.K.* (2015) MET18 Connects the Cytosolic Iron-Sulfur Cluster Assembly Pathway to Active DNA Demethylation in Arabidopsis. PLoS Genetics 11, e1005559

[2]. Li Y.#, Duan C.G.#, Zhu X., Qian W. and Zhu J.K.* (2015) A DNA ligase required for active DNA demethylation and genomic imprinting in Arabidopsis. Cell Research (#：Co-first author)

[3]. Duan C.G.#, Zhang H.#, Tang K.#, Zhu X., Qian W., Hou Y.J., Wang B., Lang Z., Zhao Y., Wang X., Wang P., Zhou J., Liang G., Liu N., Wang C., Zhu J.K.* (2014) Specific but Interdependent Functions for Arabidopsis AGO4 and AGO6 in RNA-directed DNA Methylation. EMBO Journal 34(5): 581-592

[4]. Wang, X.#, Duan, C.G.#, Tang, K., Wang, B., Zhang, H., Lei, M., Lu, K., Mangrauthia, S.K., Wang, P., Zhu, G., Zhao Y and Zhu J.K.* (2013). RNA-binding protein regulates plant DNA methylation by controlling mRNA processing at the intronic heterochromatin- containing gene IBM1. PNAS 110(38): 15467-15472 (#：Co-first author)

[5]. Feng, L.#, Duan, C.G.# and Guo, H.S.* (2013). Inhibition of in vivo Slicer activity of Argonaute protein 1 by the viral 2b protein independent of its dsRNA-binding function. Molecular Plant Pathology 14, 617-622. (#：Co-first author)

[6]. Duan, C.G.#, Fang, Y.Y.#, Zhou, B.J., Zhao, J.H., Hou, W.N., Zhu, H., Ding, S.W., and Guo, H.S.* (2012). Suppression of Arabidopsis ARGONAUTE1-mediated slicing, transgene-induced RNA silencing, and DNA methylation by distinct domains of the Cucumber mosaic virus 2b protein. Plant Cell 24, 259-274.

[7]. Duan, C.G., Wang, C.H., and Guo, H.S.* (2012). Application of RNA silencing to plant disease resistance. Silence 3: 5.

[8]. Hou, W.N.#, Duan, C.G.#, Fang, R.X., Zhou, X.Y., and Guo, H.S.* (2011). Satellite RNA reduces expression of the 2b suppressor protein resulting in the attenuation of symptoms caused by Cucumber mosaic virus infection. Molecular Plant Pathology 12, 595-605. (#：Co-first author)

[9]. Duan, C.G., Wang, C.H., Fang, R.X., and Guo, H.S.* (2008). Artificial MicroRNAs highly accessible to targets confer efficient virus resistance in plants. Journal of Virology 82, 11084-11095.

[10].            Duan C.G., Wang C.H. & Guo H.S. (2008). Delayed resistance to Cucumber Mosaic Virus mediated by 3’UTR-derived hairpin RNA. Chinese Science Bulletin 53 (21): 3301-3310

[11].            Du, Q.S.*, Duan, C.G.*, Zhang, Z.H.*, Fang, Y.Y., Fang, R.X., Xie, Q., and Guo, H.S. (2007). DCL4 targets Cucumber mosaic virus satellite RNA at novel secondary structures. Journal of Virology 81, 9142-9151. (#：Co-first author)