Research InterestsMy laboratory is interested in characterizing chromatin proteins to decipher their functions in chromatin dynamics and gene regulation and implications in human diseases.
Affiliations: Principal Investigator, Chromatin Biology and Epigenetics, Structural Genomics Consortium, University of Toronto
Courses Taught: PSL350 and PSL299
Keywords: Structural biology, epigenetics, chromatin signaling, biochemistry, proteomics, and chemical biology
Detailed Description: My lab aims to characterize chromatin proteins by X-ray crystallography in combination with other biochemical and biophysical techniques. Research in the chromatin structural biology group consists of:
1) Chromatin modifying enzymes: Chromatin structure is very dynamic, and is governed by different chromatin modifying activities such as: DNA modification, histone modification, and ATP-dependent chromatin remodeling. My laboratory is trying to understand the mechanisms of catalysis and inhibition of these chromatin modifying enzymes.
2) Regulation and recruitment of chromatin modifying activities: Regulation and recruitment of chromatin-modifying activities is critical for establishing and maintaining normal gene expression patterns, and aberrant gene expression is linked to many human diseases, such as various genetic diseases and cancers. Chromatin-modifying activities have been relatively well characterized, but the regulation and recruitment mechanisms of chromatin-modifying activities are poorly understood. One major focus of my laboratory is to identify and characterize the recruitment and regulation mechanisms of the chromatin modifying activities.
3). Structure-Based Drug Discovery: Epigenetic abnormalities play an important role in the pathogenesis of cancer and other genetic diseases. Therefore, proteins involved in chromatin modifications are attractive therapeutic targets for drug design. We are screening and designing small molecules that can inhibit chromatin-regulating proteins in collaboration with medicinal chemists.
Procedures: mass spectrometry, proteomics, western blot
Amplifier, Benchtop Centifuge, Culture hood, Culture Incubators, HPLC, Low- and High speed centrifuge, Mass Spectrometer, Microwave Oven, Mini Vortexer, Plate Reader, Setups for electropherosis, Stirrer/Hot Plate, Water Baths
Chao Xu (PDF)
Cheng Dong (PDF)
Heng Zhang (PDF)
Publications and Awards
- Xu C, Wang X, Liu K, Roundtree IA, Tempel W, Li Y, Lu Z, He C, Min J. Structural basis for selective binding of m6A RNA by the YTHDC1 YTH domain. Nat Chem Biol. 2014 Nov 1;10(11):927-9.
- Ni Z, Xu C, Guo X, Hunter GO, Kuznetsova OV, Tempel W, Marcon E, Zhong G, Guo H, Kuo WH, Li J, Young P, Olsen JB, Wan C, Loppnau P, El Bakkouri M, Senisterra GA, He H, Huang H, Sidhu SS, Emili A, Murphy S, Mosley AL, Arrowsmith CH, Min J, Greenblatt JF. RPRD1A and RPRD1B are human RNA polymerase II C-terminal domain scaffolds for Ser5 dephosphorylation. Nat Struct Mol Biol. 2014 Aug 1;21(8):686-695.
- Qin S, Liu Y, Tempel W, Eram MS, Bian C, Liu K, Senisterra G, Crombet L, Vedadi M, Min J. Structural basis for histone mimicry and hijacking of host proteins by influenza virus protein NS1. Nat Commun. 2014 May 23;5:3952.
- Alpatov R, Lesch BJ, Nakamoto-Kinoshita M, Blanco A, Chen S, Stützer A, Armache KJ, Simon MD, Xu C, Ali M, Murn J, Prisic S, Kutateladze TG, Vakoc CR, Min J, Kingston RE, Fischle W, Warren ST, Page DC, Shi Y. A Chromatin-Dependent Role of the Fragile X Mental Retardation Protein FMRP in the DNA Damage Response. Cell. 2014 May 8;157(4):869-81.
- Xu Y, Xu C, et al. (2012) Tet3 CXXC Domain and Dioxygenase Activity Cooperatively Regulate Key Genes for Xenopus Eye and Neural Development. Cell 151(6):1200-13.
- Zheng W, Ibáñez G, Wu H, Blum G, Zeng H, Dong A, Li F, Hajian T, Allali-Hassani A, Amaya MF, Siarheyeva A, Yu W, Brown PJ, Schapira M, Vedadi M, Min J, Luo M (2012) Sinefungin derivatives as inhibitors and structure probes of protein lysine methyltransferase SETD2. J Am Chem Soc 134(43):18004-14.
- Xu C, Jin J, Bian C, Lam R, Tian R, Weist R, You L, Nie J, Bochkarev A, Tempel W, Tan CS, Wasney GA, Vedadi M, Gish GD, Arrowsmith CH, Pawson T, Yang XJ, Min J (2012) Sequence-Specific Recognition of a PxLPxI/L Motif by an Ankyrin Repeat Tumbler Lock. Science Signaling 5(226):ra39.
- Bian C, Xu C, Ruan J, Lee KK, Burke TL, Tempel W, Barsyte D, Li J, Wu M, Zhou BO, Fleharty BE, Paulson A, Allali-Hassani A, Zhou JQ, Mer G, Grant PA, Workman JL, Zang J, Min J (2011) Sgf29 Binds Histone H3K4me2/3 and Is Required For SAGA Complex Recruitment and Histone H3 Acetylation. EMBO J 30(14):2829-42
- Xu C, Bian C, Lam R, Dong A, Min J (2011) The structural basis for selective binding of non-methylated CpG islands by the CFP1 CXXC domain. Nature Communications 2:227.
- Adams-Cioaba MA, Krupa JC, Xu C, Mort JS, Min J (2011) Structural basis for the recognition and cleavage of histone H3 by cathepsin L. Nature Communications 2:197.
- Xu C, Bian C, Yang W, Galka M, Ouyang H, Chen C, Qiu W, Liu H, Jones AE, Mackenzie F, Pan P, Li SS, Wang H, Min J (2010) Binding of different histone marks differentially regulates the activity and specificity of polycomb repressive complex 2 (PRC2). Proc Natl Acad Sci USA 107(45):19266-71.
- Liu K, Chen C, Guo Y, Lam R, Bian C, Xu C, Zhao DY, Jin J, MacKenzie F, Pawson T, Min J (2010) Structural basis for recognition of arginine methylated Piwi proteins by the extended Tudor domain. Proc Natl Acad Sci USA 107(43):18398-403.