
Xing Zhang
Department of Epigenetics and Molecular Carcinogenesis, Division of Discovery Science
Present Title & Affiliation
Dual/Joint/Adjunct Appointment
Associate Professor, Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX
Education & Training
Degree-Granting Education
1995 | SUNY Stony Brook, Stony Brook, New York, US, Genetics, Ph.D |
1985 | Fudan University, Shanghai, CN, Microbiology, BS |
Experience & Service
Academic Appointments
Associate Professor, Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 2016 - 2019
Assistant Professor, Emory University School of Medicine, Atlanta, GA, 1997 - 2016
Selected Publications
Peer-Reviewed Articles
- Zhou J, Chen Q, Ren R, Yang J, Liu B, Horton JR, Chang C, Li C, Maksoud L, Yang Y, Rotili D, Jain AK, Zhang X, Blumenthal RM, Chen T, Gao Y, Valente S, Mai A, Cheng X. Quinoline-based compounds can inhibit diverse enzymes that act on DNA. Cell Chem Biol, 2024. e-Pub 2024. PMID: 39437789.
- Hardikar S, Ren R, Ying Z, Zhou J, Horton JR, Bramble MD, Liu B, Lu Y, Liu B, Coletta LD, Shen J, Dan J, Zhang X, Cheng X, Chen T. The ICF syndrome protein CDCA7 harbors a unique DNA binding domain that recognizes a CpG dyad in the context of a non-B DNA. Sci Adv 10(34):eadr0036, 2024. e-Pub 2024. PMID: 39178265.
- Yang J, Horton JR, Liu B, Corces VG, Blumenthal RM, Zhang X, Cheng X. Structures of CTCF-DNA complexes including all 11 zinc fingers. Nucleic Acids Res 51(16):8447-8462, 2023. e-Pub 2023. PMID: 37439339.
- Zhou J, Horton JR, Kaur G, Chen Q, Li X, Mendoza F, Wu T, Blumenthal RM, Zhang X, Cheng X. Biochemical and structural characterization of the first-discovered metazoan DNA cytosine-N4 methyltransferase from the bdelloid rotifer Adineta vaga. J Biol Chem 299(8):105017, 2023. e-Pub 2023. PMID: 37414145.
- Chen Q, Liu B, Zeng Y, Hwang JW, Dai N, Corrêa IR, Estecio MR, Zhang X, Santos MA, Chen T, Cheng X. GSK-3484862 targets DNMT1 for degradation in cells. NAR Cancer 5(2):zcad022, 2023. e-Pub 2023. PMID: 37206360.
- Zhou J, Deng Y, Iyamu ID, Horton JR, Yu D, Hajian T, Vedadi M, Rotili D, Mai A, Blumenthal RM, Zhang X, Huang R, Cheng X. Comparative Study of Adenosine Analogs as Inhibitors of Protein Arginine Methyltransferases and a Clostridioides difficile-Specific DNA Adenine Methyltransferase. ACS Chem Biol 18(4):734-745, 2023. e-Pub 2023. PMID: 37082867.
- Horton JR, Zhou J, Chen Q, Zhang X, Bedford MT, Cheng X. A complete methyl-lysine binding aromatic cage constructed by two domains of PHF2. J Biol Chem 299(2):102862, 2023. e-Pub 2023. PMID: 36596360.
- Ren R, Horton JR, Chen Q, Yang J, Liu B, Huang Y, Blumenthal RM, Zhang X, Cheng X. Structural basis for transcription factor ZBTB7A recognition of DNA and effects of ZBTB7A somatic mutations that occur in human acute myeloid leukemia. J Biol Chem 299(2):102885, 2023. e-Pub 2023. PMID: 36626981.
- Kaur G, Ren R, Hammel M, Horton JR, Yang J, Cao Y, He C, Lan F, Lan X, Blobel GA, Blumenthal RM, Zhang X, Cheng X. Allosteric autoregulation of DNA binding via a DNA-mimicking protein domain: a biophysical study of ZNF410-DNA interaction using small angle X-ray scattering. Nucleic Acids Res 51(4):1674-1686, 2023. e-Pub 2023. PMID: 36660822.
- Zhou J, Horton JR, Menna M, Fiorentino F, Ren R, Yu D, Hajian T, Vedadi M, Mazzoccanti G, Ciogli A, Weinhold E, Hüben M, Blumenthal RM, Zhang X, Mai A, Rotili D, Cheng X. Systematic Design of Adenosine Analogs as Inhibitors of a Clostridioides difficile-Specific DNA Adenine Methyltransferase Required for Normal Sporulation and Persistence. J Med Chem 66(1):934-950, 2023. e-Pub 2023. PMID: 36581322.
- Horton JR, Pathuri S, Wong K, Ren R, Rueda L, Fosbenner DT, Heerding DA, McCabe MT, Pappalardi MB, Zhang X, King BW, Cheng X. Structural characterization of dicyanopyridine containing DNMT1-selective, non-nucleoside inhibitors. Structure 30(6):793-802.e5, 2022. e-Pub 2022. PMID: 35395178.
- Yu D, Zhou J, Chen Q, Wu T, Blumenthal RM, Zhang X, Cheng X. Enzymatic Characterization of In Vitro Activity of RNA Methyltransferase PCIF1 on DNA. Biochemistry 61(11):1005-13. e-Pub 2022. PMID: 35605980.
- Yang J, Gupta E, Horton JR, Blumenthal RM, Zhang X, Cheng X. Differential ETS1 binding to T:G mismatches within a CpG dinucleotide contributes to C-to-T somatic mutation rate of the IDH2 hotspot at codon Arg140. DNA Repair (Amst) 113:103306. e-Pub 2022. PMID: 35255310.
- Yu D, Dai N, Wolf EJ, Corrêa IR, Zhou J, Wu T, Blumenthal RM, Zhang X, Cheng X. Enzymatic characterization of mRNA cap adenosine-N6 methyltransferase PCIF1 activity on uncapped RNAs. J Biol Chem 298(4):101751. e-Pub 2022. PMID: 35189146.
- Yu D, Horton JR, Yang J, Hajian T, Vedadi M, Sagum CA, Bedford MT, Blumenthal RM, Zhang X, Cheng X. Human MettL3-MettL14 RNA adenine methyltransferase complex is active on double-stranded DNA containing lesions. Nucleic Acids Res 49(20):11629-11642, 2021. e-Pub 2021. PMID: 34086966.
- Pappalardi MB, Keenan K, Cockerill M, Kellner WA, Stowell A, Sherk C, Wong K, Pathuri S, Briand J, Steidel M, Chapman P, Groy A, Wiseman AK, McHugh CF, Campobasso N, Graves AP, Fairweather E, Werner T, Raoof A, Butlin RJ, Rueda L, Horton JR, Fosbenner DT, Zhang C, Handler JL, Muliaditan M, Mebrahtu M, Jaworski JP, McNulty DE, Burt C, Eberl HC, Taylor AN, Ho T, Merrihew S, Foley SW, Rutkowska A, Li M, Romeril SP, Goldberg K, Zhang X, Kershaw CS, Bantscheff M, Jurewicz AJ, Minthorn E, Grandi P, Patel M, Benowitz AB, Mohammad HP, Gilmartin AG, Prinjha RK, Ogilvie D, Carpenter C, Heerding D, Baylin SB, Jones PA, Cheng X, King BW, Luengo JI, Jordan AM, Waddell I, Kruger RG, McCabe MT. Discovery of a first-in-class reversible DNMT1-selective inhibitor with improved tolerability and efficacy in acute myeloid leukemia. Nat Cancer 2(10):1002-1017, 2021. e-Pub 2021. PMID: 34790902.
- Zhou J, Horton JR, Yu D, Ren R, Blumenthal RM, Zhang X, Cheng X. Repurposing epigenetic inhibitors to target the Clostridioides difficile-specific DNA adenine methyltransferase and sporulation regulator CamA. Epigenetics:1-12. e-Pub 2021. PMID: 34523387.
- Zhou J, Horton JR, Blumenthal RM, Zhang X, Cheng X. Clostridioides difficile specific DNA adenine methyltransferase CamA squeezes and flips adenine out of DNA helix. Nat Commun 12(1):3436, 2021. e-Pub 2021. PMID: 34103525.
- Yang J, Horton JR, Akdemir KC, Li J, Huang Y, Kumar J, Blumenthal RM, Zhang X, Cheng X. Preferential CEBP binding to T:G mismatches and increased C-to-T human somatic mutations. Nucleic Acids Res 49(9):5084-5094, 2021. e-Pub 2021. PMID: 33877329.
- Yu D, Kaur G, Blumenthal RM, Zhang X, Cheng X. Enzymatic characterization of three human RNA adenosine methyltransferases reveals diverse substrate affinities and reaction optima. J Biol Chem 296:100270, 2021. e-Pub 2021. PMID: 33428944.
- Zeng Y, Ren R, Kaur G, Hardikar S, Ying Z, Babcock L, Gupta E, Zhang X, Chen T, Cheng X. The inactive Dnmt3b3 isoform preferentially enhances Dnmt3b-mediated DNA methylation. Genes Dev 34(21-22):1546-1558, 2020. e-Pub 2020. PMID: 33004415.
- Woodcock CB, Horton JR, Zhou J, Bedford MT, Blumenthal RM, Zhang X, Cheng X. Biochemical and structural basis for YTH domain of human YTHDC1 binding to methylated adenine in DNA. Nucleic Acids Res 48(18):10329-10341, 2020. e-Pub 2020. PMID: 32663306.
- Dai S, Holt MV, Horton JR, Woodcock CB, Patel A, Zhang X, Young NL, Wilkinson AW, Cheng X. Characterization of SETD3 methyltransferase-mediated protein methionine methylation. J Biol Chem 295(32):10901-10910, 2020. e-Pub 2020. PMID: 32503840.
- Kumar J, Kaur G, Ren R, Lu Y, Lin K, Li J, Huang Y, Patel A, Barton MC, Macfarlan T, Zhang X, Cheng X. KRAB domain of ZFP568 disrupts TRIM28-mediated abnormal interactions in cancer cells. NAR Cancer 2(2):zcaa007, 2020. e-Pub 2020. PMID: 32743551.
- Mahgoub M, Paiano J, Bruno M, Wu W, Pathuri S, Zhang X, Ralls S, Cheng X, Nussenzweig A, Macfarlan TS. Dual histone methyl reader ZCWPW1 facilitates repair of meiotic double strand breaks in male mice. Elife 9, 2020. e-Pub 2020. PMID: 32352380.
- Dai S, Horton JR, Wilkinson AW, Gozani O, Zhang X, Cheng X. An engineered variant of SETD3 methyltransferase alters target specificity from histidine to lysine methylation. J Biol Chem 295(9):2582-2589, 2020. e-Pub 2020. PMID: 31911441.
- Horton JR, Yang J, Zhang X, Petronzio T, Fomenkov A, Wilson GG, Roberts RJ, Cheng X. Structure of HhaI endonuclease with cognate DNA at an atomic resolution of 1.0 Å. Nucleic Acids Res. e-Pub 2019. PMID: 31879785.
- Horton JR, Woodcock CB, Opot SB, Reich NO, Zhang X, Cheng X. The cell cycle-regulated DNA adenine methyltransferase CcrM opens a bubble at its DNA recognition site. Nat Commun 10(1):4600, 2019. e-Pub 2019. PMID: 31601797.
- Ren R, Hardikar S, Horton JR, Lu Y, Zeng Y, Singh AK, Lin K, Coletta LD, Shen J, Lin Kong CS, Hashimoto H, Zhang X, Chen T, Cheng X. Structural basis of specific DNA binding by the transcription factor ZBTB24. Nucleic Acids Res 47(16):8388-8398, 2019. e-Pub 2019. PMID: 31226215.
- Yang J, Horton JR, Li J, Huang Y, Zhang X, Blumenthal RM, Cheng X. Structural basis for preferential binding of human TCF4 to DNA containing 5-carboxylcytosine. Nucleic Acids Res 47(16):8375-8387, 2019. e-Pub 2019. PMID: 31081034.
- Dai S, Horton JR, Woodcock CB, Wilkinson AW, Zhang X, Gozani O, Cheng X. Structural basis for the target specificity of actin histidine methyltransferase SETD3. Nat Commun 10(1):3541, 2019. e-Pub 2019. PMID: 31388018.
- Yang J, Horton JR, Wang D, Ren R, Li J, Sun D, Huang Y, Zhang X, Blumenthal RM, Cheng X. Structural basis for effects of CpA modifications on C/EBPβ binding of DNA. Nucleic Acids Res 47(4):1774-1785, 2019. e-Pub 2019. PMID: 30566668.
- Wilkinson AW, Diep J, Dai S, Liu S, Ooi YS, Song D, Li TM, Horton JR, Zhang X, Liu C, Trivedi DV, Ruppel KM, Vilches-Moure JG, Casey KM, Mak J, Cowan T, Elias JE, Nagamine CM, Spudich JA, Cheng X, Carette JE, Gozani O. SETD3 is an actin histidine methyltransferase that prevents primary dystocia. Nature 565(7739):372-376, 2019. e-Pub 2019. PMID: 30626964.
- Woodcock CB, Yu D, Hajian T, Li J, Huang Y, Dai N, Corrêa IR, Wu T, Vedadi M, Zhang X, Cheng X. Human MettL3-MettL14 complex is a sequence-specific DNA adenine methyltransferase active on single-strand and unpaired DNA in vitro. Cell Discov 5:63, 2019. e-Pub 2019. PMID: 31885874.
- Woodcock CB, Yu D, Zhang X, Cheng X. Human HemK2/KMT9/N6AMT1 is an active protein methyltransferase, but does not act on DNA in vitro, in the presence of Trm112. Cell Discov 5:50, 2019. e-Pub 2019. PMID: 31632689.
- Horton JR, Woodcock CB, Chen Q, Liu X, Zhang X, Shanks J, Rai G, Mott BT, Jansen DJ, Kales SC, Henderson MJ, Cyr M, Pohida K, Hu X, Shah P, Xu X, Jadhav A, Maloney DJ, Hall MD, Simeonov A, Fu H, Vertino PM, Cheng X. Structure-Based Engineering of Irreversible Inhibitors against Histone Lysine Demethylase KDM5A. J Med Chem 61(23):10588-10601, 2018. e-Pub 2018. PMID: 30392349.
- Wang D, Horton JR, Zheng Y, Blumenthal RM, Zhang X, Cheng X. Role for first zinc finger of WT1 in DNA sequence specificity: Denys-Drash syndrome-associated WT1 mutant in ZF1 enhances affinity for a subset of WT1 binding sites. Nucleic Acids Res 46(8):3864-3877, 2018. e-Pub 2018. PMID: 29294058.
- Horton JR, Liu X, Wu L, Zhang K, Shanks J, Zhang X, Rai G, Mott BT, Jansen DJ, Kales SC, Henderson MJ, Pohida K, Fang Y, Hu X, Jadhav A, Maloney DJ, Hall MD, Simeonov A, Fu H, Vertino PM, Yan Q, Cheng X. Insights into the Action of Inhibitor Enantiomers against Histone Lysine Demethylase 5A. J Med Chem 61(7):3193-3208, 2018. e-Pub 2018. PMID: 29537847.
- Patel A, Yang P, Tinkham M, Pradhan M, Sun MA, Wang Y, Hoang D, Wolf G, Horton JR, Zhang X, Macfarlan T, Cheng X. DNA Conformation Induces Adaptable Binding by Tandem Zinc Finger Proteins. Cell 173(1):221-233.e12, 2018. e-Pub 2018. PMID: 29551271.
- Murray IA, Morgan RD, Luyten Y, Fomenkov A, Corrêa IR, Dai N, Allaw MB, Zhang X, Cheng X, Roberts RJ. The non-specific adenine DNA methyltransferase M.EcoGII. Nucleic Acids Res 46(2):840-848, 2018. e-Pub 2018. PMID: 29228259.
- Patel A, Zhang X, Blumenthal RM, Cheng X. Structural basis of human PR/SET domain 9 (PRDM9) allele C-specific recognition of its cognate DNA sequence. J Biol Chem 292(39):15994-16002, 2017. e-Pub 2017. PMID: 28801461.
- Hashimoto H, Wang D, Horton JR, Zhang X, Corces VG, Cheng X. Structural Basis for the Versatile and Methylation-Dependent Binding of CTCF to DNA. Mol Cell 66(5):711-720.e3, 2017. e-Pub 2017. PMID: 28529057.
- Wang D, Hashimoto H, Zhang X, Barwick BG, Lonial S, Boise LH, Vertino PM, Cheng X. MAX is an epigenetic sensor of 5-carboxylcytosine and is altered in multiple myeloma. Nucleic Acids Res 45(5):2396-2407, 2017. e-Pub 2017. PMID: 27903915.
- Hong S, Wang D, Horton JR, Zhang X, Speck SH, Blumenthal RM, Cheng X. Methyl-dependent and spatial-specific DNA recognition by the orthologous transcription factors human AP-1 and Epstein-Barr virus Zta. Nucleic Acids Res 45(5):2503-2515, 2017. e-Pub 2017. PMID: 28158710.
- Hashimoto H, Zhang X, Zheng Y, Wilson GG, Cheng X. Denys-Drash syndrome associated WT1 glutamine 369 mutants have altered sequence-preferences and altered responses to epigenetic modifications. Nucleic Acids Res 44(21):10165-10176, 2016. e-Pub 2016. PMID: 27596598.
- Hashimoto H, Wang D, Steves AN, Jin P, Blumenthal RM, Zhang X, Cheng X. Distinctive Klf4 mutants determine preference for DNA methylation status. Nucleic Acids Res 44(21):10177-10185, 2016. e-Pub 2016. PMID: 27596594.
- Horton JR, Liu X, Gale M, Wu L, Shanks JR, Zhang X, Webber PJ, Bell JSK, Kales SC, Mott BT, Rai G, Jansen DJ, Henderson MJ, Urban DJ, Hall MD, Simeonov A, Maloney DJ, Johns MA, Fu H, Jadhav A, Vertino PM, Yan Q, Cheng X. Structural Basis for KDM5A Histone Lysine Demethylase Inhibition by Diverse Compounds. Cell Chem Biol 23(7):769-781, 2016. e-Pub 2016. PMID: 27427228.
- Horton JR, Engstrom A, Zoeller EL, Liu X, Shanks JR, Zhang X, Johns MA, Vertino PM, Fu H, Cheng X. Characterization of a Linked Jumonji Domain of the KDM5/JARID1 Family of Histone H3 Lysine 4 Demethylases. J Biol Chem 291(6):2631-46, 2016. e-Pub 2016. PMID: 26645689.
- Patel A, Horton JR, Wilson GG, Zhang X, Cheng X. Structural basis for human PRDM9 action at recombination hot spots. Genes Dev 30(3):257-65, 2016. e-Pub 2016. PMID: 26833727.
- Patel A, Hashimoto H, Zhang X, Cheng X. Characterization of How DNA Modifications Affect DNA Binding by C2H2 Zinc Finger Proteins. Methods Enzymol 573:387-401, 2016. e-Pub 2016. PMID: 27372763.
- Hashimoto H, Pais JE, Dai N, Corrêa IR, Zhang X, Zheng Y, Cheng X. Structure of Naegleria Tet-like dioxygenase (NgTet1) in complexes with a reaction intermediate 5-hydroxymethylcytosine DNA. Nucleic Acids Res 43(22):10713-21, 2015. e-Pub 2015. PMID: 26323320.
- Horton JR, Zhang X, Blumenthal RM, Cheng X. Structures of Escherichia coli DNA adenine methyltransferase (Dam) in complex with a non-GATC sequence: potential implications for methylation-independent transcriptional repression. Nucleic Acids Res 43(8):4296-308, 2015. e-Pub 2015. PMID: 25845600.
Other Articles
- Zhang X, Blumenthal RM, Cheng X DNA-binding proteins from MBD through ZF to BEN: recognition of cytosine methylation status by one arginine with two conformations. Nucleic Acids Res 52(19):11442-11454, 2024. PMID: 39329271.
- Zhang, X, Blumenthal, RM, Cheng, X Keep Fingers on the CpG Islands. Epigenomes 8(2), 2024. PMID: 38920624.
- Zhang X, Blumenthal RM, Cheng X Updated understanding of the protein-DNA recognition code used by C2H2 zinc finger proteins. Curr Opin Struct Biol 87:102836. PMID: 38754172.
- Zhang X, Xia F, Zhang X, Blumenthal RM, Cheng X C2H2 zinc finger transcription factors associated with hemoglobinopathies. J Mol Biol 436(7):168343, 2024. PMID: 37924864.
- Zhang X, Blumenthal RM, Cheng X A Role for N6-Methyladenine in DNA Damage Repair. Trends Biochem Sci 46(3):175-183, 2021. PMID: 33077363.
- Woodcock CB, Horton JR, Zhang X, Blumenthal RM, Cheng X Beta class amino methyltransferases from bacteria to humans: evolution and structural consequences. Nucleic Acids Res 48(18):10034-10044, 2020. PMID: 32453412.
- Yang J, Zhang X, Blumenthal RM, Cheng X Detection of DNA Modifications by Sequence-Specific Transcription Factors. J Mol Biol. PMID: 31626807.
- Ren R, Horton JR, Zhang X, Blumenthal RM, Cheng X Detecting and interpreting DNA methylation marks. Curr Opin Struct Biol 53:88-99, 2018. PMID: 30031306.
- Hashimoto H, Zhang X, Vertino PM, Cheng X The Mechanisms of Generation, Recognition, and Erasure of DNA 5-Methylcytosine and Thymine Oxidations. J Biol Chem 290(34):20723-33, 2015. PMID: 26152719.
Grant & Contract Support
Date: | 2023 - 2026 |
Title: | Mutual reinforcement between somatic mutations and transcription factors in clonal hematopoiesis |
Funding Source: | NIH |
Role: | Co-I |
ID: | R01DK132286-01A1 |
Date: | 2020 - 2024 |
Title: | Epigenetic regulations of DNA and histone methylation and deMethylation: Structures and Mechanisms |
Funding Source: | NIH/NIGMS |
Role: | Co-I |
ID: | R35 GM134744 |
Patient Reviews
CV information above last modified March 19, 2025