University of California, Riverside

Profiles

Jikui Song

Professor

Biochemistry Dept

CNAS Deans Office Dept

jikui.song@ucr.edu

(951) 827-4221

Short URL https://profiles.ucr.edu/jikui.song
Lab Website Song Lab-Structural Biology of Epigenetics

Biography

Dr. Song obtained his Ph.D. degree in biochemistry from University of Wisconsin-Madison in 2002 with Prof. John L Markley. His doctoral work focused on investigation of protein structure-function relationships using NMR spectroscopy. After that, he joined the Center for Eukaryotic Structural Genomics (CESG) as research scientist to engage in NMR-based structural proteomics. During 2007-2011, He was a postdoctoral fellow in Dr. Dinshaw J Patel’s laboratory at Memorial Sloan-Kettering Cancer Center, where he performed structural and biophysical characterizations of various epigenetic complexes, including “readers” and “writers” of histone marks and/or DNA methylation. In 2012, he joined the Department of Biochemistry at UC Riverside as assistant professor. Since then, his research has continued to focus on mechanistic understanding of macromolecular machineries involved in epigenetic regulation or host-pathogen interactions.  

Research Interests:

Our research program focuses on mechanistic understanding of protein machineries mediating key cellular activities, including epigenetic regulation and host-pathogen interaction. Epigenetics is a rapidly developing field that investigates how inheritable information beyond DNA sequence, such as chromatin modifications and non-coding RNAs, influences chromatin structure and function. Epigenetic modifications, including DNA methylation and histone modifications, regulate a broad spectrum of nuclear functions, including transcription, DNA replication and repair. Genomic patterns of DNA methylation and histone modifications are dynamically regulated by a set of chromatin modifiers, whose dysregulation is linked to many human diseases, such as cancer. We are particularly interested in mechanistic understanding of how DNA methylation machineries establish and maintain specific DNA methylation patterns, and how different histone modifications are recognized by distinct “reader” proteins to initiate downstream signaling. In addition, we are interested in understanding how pathogen-host interactions influence cellular activities, through characterizations of protein complexes that are important for pathogen infection or host immunity. By using X-ray crystallography and NMR spectroscopy, combined with biochemical and cellular assays, we aim to elucidate the molecular mechanisms underlying these molecular regulations at atomic resolution.

Awards

  • Basil O’Connor Starter Scholar Research Award, March of Dimes Foundation
  • Robert T. Poe Faculty Development Grant, Chinese American Faculty Association of Southern California
  • Regents’ Faculty Fellowship, University of California, Riverside
  • Hellman Fellowship, Hellman Family Foundation
  • California Cancer Research Coordination Committee Grant
  • Kimmel Scholar, Sidney Kimmel Foundation for Cancer Research

Publications

Selected Publications (#Corresponding author)
  • Zhang ZM, Lu R, Wang P, Yu Y, Chen D, Gao L, Liu S, Ji D, Rothbart SB, Wang Y, Wang GG#, Song J#. Structural basis for DNMT3A-mediated de novo DNA methylation. Nature. 2018; 554: 387-391.
  • Gao L, Tan XF, Zhang S, Wu T, Zhang ZM, Ai HW, Song J#. An Intramolecular Interaction of UHRF1 Reveals Dual Control for Its Histone Association. Structure. 2018; 26: 304-311. PMID: 29395786
  • Zhang ZM, Ma KW, Gao L, Hu Z, Schwizer S, Ma W#, Song J#.  Mechanism of host substrate acetylation by a YopJ family effector. Nature Plants. (2017) 3:17115. PMID: 28737762
  • Wang B, Tan XF, Thurmond S, Zhang ZM, Lin A, Hai R#, Song J#. The structure of Zika virus NS5 reveals a conserved domain conformation. Nature Communications. (2017) 8:14763. PMID:28345600

  • Zhang ZM, Ma KW, Yuan S, Luo Y, Jiang S, Hawara E, Pan S, Ma W#, Song J#. Structure of a pathogen effector reveals enzymatic mechanism of a novel acetyltransferase family. Nature Structural & Molecular Biology. (2016) 23:847-52.

  • Harter MR, Liu CD, Shen CL, Gonzalez-Hurtado E, Zhang ZM, Xu M, Martinez E, Peng CW#, Song J#.  BS69/ZMYND11 C-terminal domains bind and inhibit EBNA2. Plos Pathog. (2016) 12(2): e1005414.

  • Jin SG, Zhang ZM, Dunwell TL, Harter MR, Wu X, Johnson J, Li Z, Liu J, Szabo PE, Lu Q, Xu GL, Song J#, Pfeifer GP#. Tet3 reads 5-carboxylcytosine through its CXXC domain and is a potential guardian against neurodegeneration. Cell Rep. (2016) 14:493-505. PubMed PMID: 26774490.

  • Zhang ZM, Rothbart SB, Allison DF, Cai Q, Harrison JS, Li L, Wang Y, Strahl BD, Wang GG, Song J#. An allosteric interaction links USP7 to deubiquitination  and chromatin targeting of UHRF1. Cell Rep. (2015) 12:1400-6.

  • Zhang ZM, Liu S, Lin K, Luo Y, Perry JJ, Wang Y, Song J#. Crystal Structure of Human DNA Methyltransferase 1. J. Mol. Biol. (2015) 427: 2520-31.

  • Zhang W, Sankaran S, Gozani O, Song J#. A Meier-Gorlin Syndrome Mutation Impairs the ORC1-Nucleosome Association. ACS Chem. Biol. 2015 10: 1176-80.
  • Cai L, Rothbart SB, Lu R, Xu B, Chen WY, Tripathy A, Rockowitz S, Zheng D, Patel DJ, Allis CD, Strahl BD, Song J#, Wang GG#. An H3K36 Methylation-Engaging Tudor Motif of Polycomb-like Proteins Mediates PRC2 Complex Targeting. Mol. Cell(2013) 49: 1-12.
  • Kuo AJ*, Song J*, Cheung P*, Ishibe-Murakami S, Yamazoe S, Chen JK, Patel DJ, Gozani, O. ORC1 BAH domain links dimethylation of H4K20 to DNA replication licensing and Meier-Gorlin syndrome. Nature. 2012, 484(7392):115-9. (* These authors have contributed equally to this work)
  • Song J, Teplova M, Ishibe-Murakami S, Patel, DJ. Structure-based Mechanistic Insights into DNMT1-mediated Maintenance DNA methylation. Science 2012, 335(6069):709-712.
  • Song J, Rechkoblit O, Bestor TH, Patel DJ. Structure of DNMT1-DNA complex reveals a role for autoinhibition in maintenance DNA methylation. Science 2011, 331(6020):1036-40.
  • Teplova M, Song J, Gaw HY, Teplov A, Patel DJ. Structural insights into RNA recognition by the Alternate-splicing Regulator CUG Binding Protein 1. Structure 2010, 18(10):1364-77.
  • Wang Z*, Song J*, Milne TA, Wang GG, Li H, Allis CD, Patel DJ. Molecular Events Underlying MLL1 Regulation by H3K4me3 Readout and Cyclophilin-mediated Proline Isomerization. Cell 2010, 141(7):1183-94. (* These authors have contributed equally to this work)
  • Wang GG, Song J, Wang Z, Dormann HL, Casadio F, Li H, Luo JL, Patel DJ, Allis CD. Haematopoietic Malignancies Caused by Dysregulation of a Chromatin-binding PHD Finger. Nature 2009, 459(7248): 847-51.
  • Song J*, McGivern JV*, Nichols KW, Markley JL, Sheets MD. Structural basis for RNA recognition by a type II poly(A)-binding protein. Proc. Nat l. Acad. Sci 2008, 105(40):15317-22. (* These authors have contributed equally to this work)
  • Song J, Bettendorff L., Tonelli, M., Markley JL. Structural Basis for the Catalytic Mechanism of Mammalian 25 kDa Thiamine Triphosphatase. J Biol Chem 2008, 283(16):10939-48.
  • Song J*, Guo LW*, Muradov H, Artemyev NO, Ruoho AE, Markley JL. Intrinsically disordered γ subunit of cGMP phosphodiesterase encodes functional relevant transient secondary and tertiary structures. Proc. Natl. Acad. Sci 2008, 105(5):1505-10. (* These authors have contributed equally to this work)
  • Song J, Zhao Q, Vinarov DA, Loushin Newman C, Markley JL. Solution structure of human sorting nexin 22. Protein Science 2007, 16(5):807-14.
  • Song J, Markley JL. Cautionary Tail: the presence of an N-terminal tag on dynein light-chain roadblock/LC7 affects its interaction with a functional partner. Protein Pept Letter 2007, 14(3):265-268.
  • Song J, Markley JL. Three-dimensional structure determined for a subunit of human tRNA splicing endonuclease (Sen15) reveals a novel dimeric fold. J Mol Biol 2007, 366(1):155-164.
  • Song J, Lee MS, Carlberg I, Vener AV, Markley JL. Micelle-induced folding of spinach thylakoid soluble phosphoprotein of 9 kDa and its functional implications. Biochemistry 2006, 45(51): 15633-15643.
  • Song J, Tyler RC, Lee MS, Tyler EM, Markley JL. Solution structure of isoform 1 of Roadblock/LC7, a light chain in the dynein complex. J Mol Biol 2005, 354(5):1043-1051.
  • Song J, Tyler RC, Wrobel RL, Frederick RO, Vojtek FC, Jeon WB, Lee MS, Markley JL. Solution structure of At3g04780.1-des15, an Arabidopsis thaliana ortholog of the C-terminal domain of human thioredoxin like protein. Protein Science 2005, 14(4):1059-63.
  • Zhao Q, Song J, Jin Z, Danilova V, Hellekant G, Markley JL. Probing the sweet determinants of brazzein: wild type brazzein and a tasteless variant, brazzein-ins(R18a-I18b), exhibit different pH-dependent NMR chemical shifts. Biochem Biophys Res Commun 2005, 335(1):256-263.
  • Song J, Zhao Q, Thao S, Friederick, RO, and Markley JL. Solution Structure of a Calmodulin-Like Calcium-Binding Domain from Arabidopsis thaliana. J Biomol NMR 2004, 30(4):451-6.
  • Song J, Vinarov, DA, Tyler EM, Shahan MN, Tyler RC, and Markley, JL Hypothetical Protein At2g24940.1 from Arabidopsis thaliana Adopts a Cytochrome b5 like Fold. J Biomol NMR 2004, 30(2):215-8.
  • Song J, Qasim MA, Laskowski M Jr., Markley JL. Two Conformational States of Turkey Ovomucoid at Low pH: Three-Dimensional Structures, Internal Dynamics, and Interconversion Kinetics and Thermodynamics. Biochemistry 2003, 42(21):6380-6391.
  • Song J, Markley JL. Protein Inhibitors of Serine Proteinases: Role of Backbone Structure and Dynamics in Controlling the Hydrolysis Constant. Biochemistry 2003, 42(18):5186-5194.
  • Song J, Laskowski M Jr, Qasim MA., Markley JL. NMR Determination of pKa Values for Asp, Glu, His, and Lys Mutants at each Variable Contiguous Enzyme-Inhibitor Contact Position of Turkey Ovomucoid Third Domain. Biochemistry 2003, 42(10):2847-2856.
  • Song J, Markley J.L. NMR chemical shift mapping of the binding site of a protein proteinase inhibitor: changes in the (1)H, (13)C and (15)N NMR chemical shifts of turkey ovomucoid third domain upon binding to bovine chymotrypsin A(alpha). J Mol Recognit 2001, 14(3):166-71.

Education

Ph.D., University of Wisconsin-Madison, 2002 
Assistant Researcher, University of Wisconsin-Madison, 2002-2007 
Research Associate / Senior Research Scientist at Memorial Sloan-Kettering Cancer Center in New York, 2007-2011


Departments / Programs

  • Biochemistry and Molecular Biology Graduate Program

Research Areas

  • Structural Biology
  • Biophysics
  • Epigenetic Regulation
  • Host-Pathogen Interaction
  • Drug Discovery

Office Information

Office Location: 5485 Boyce Hall
© 2018 Regents of the University of California