John R Horton, Ph.D.
Department of Epigenetics and Molecular Carcinogenesis, Division of Discovery Science
About Dr. John R Horton
I am a structural biologist with experience as an academic researcher and teacher with outstanding technical capabilities in all aspects of X-ray crystallography, molecular biology, biochemistry, and bioinformatics. My interests include understanding macromolecular structure/function in neural cellular development and differentiation in addition to determination of macromolecular complexes involved with epigenetic regulation that may have a relationship to cancer.
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Present Title & Affiliation
Primary Appointment
Associate Professor, Department of Epigenetics and Molecular Carcinogenesis, Division of Discovery Science, The University of Texas MD Anderson Cancer Center, Houston, TX
Associate Member, Department of UTHealth Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX
Associate Professor, Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
Education & Training
Postgraduate Training
| 1992-1997 | Postdoctoral, X-ray crystallography, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York |
Experience & Service
Academic Appointments
Associate Professor, Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 2017 - 2019
Assistant Professor, Emory University School of Medicine, Atlanta, GA, 1997 - 2016
Postdoctoral Scientist, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 1992 - 1997
Other Appointments/Responsibilities
Synchrotron Beamline Coordinator, State University of New York at Stony Brook and Cold Spring Harbor Laboratory, Upton, NY, 1995 - 1997
Institutional Committee Activities
Chair, RFA Progress Review Committee, 2022 - 2022
Faculty Instructor, RFA Progress Review Committee, 2022 - 2022
Honors & Awards
| 1992 | Research Fellow, Cancer Research Fund of the Damon Runyon-Walker Winchell Foundation |
| 1990 | Graduate Student Invitee/Speaker, Anomalous Phasing Techniques in Macromolecular Crystallography, Second Annual Birmingham Crystallography Workshop, University of Alabama Center for Macromolecular Crystallography |
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, A, 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 Chemical Biology 31(12):2112-2127.e6, 2024. e-Pub 2024. PMID: 39437789.
- Hardikar, S, Ren, R, Ying, Z, Zhou, J, Horton, JR, Bramble, M, 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. Science Advances 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.
- Huang P, Peslak SA, Ren R, Khandros E, Qin K, Keller CA, Giardine B, Bell HW, Lan X, Sharma M, Horton JR, Abdulmalik O, Chou ST, Shi J, Crossley M, Hardison RC, Cheng X, Blobel GA. Author Correction: HIC2 controls developmental hemoglobin switching by repressing BCL11A transcription. Nat Genet 55(9):1608, 2023. e-Pub 2023. PMID: 37524792.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Huang P, Peslak SA, Ren R, Khandros E, Qin K, Keller CA, Giardine B, Bell HW, Lan X, Sharma M, Horton JR, Abdulmalik O, Chou ST, Shi J, Crossley M, Hardison RC, Cheng X, Blobel GA. HIC2 controls developmental hemoglobin switching by repressing BCL11A transcription. Nat Genet. e-Pub 2022. PMID: 35941187.
- 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.
- 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.
- Ren R, Horton JR, Hong S, Cheng X. Recent Advances on DNA Base Flipping: A General Mechanism for Writing, Reading, and Erasing DNA Modifications. Adv Exp Med Biol 1389:295-315, 2022. e-Pub 2022. PMID: 36350515.
- 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.
- Yang Y, Ren R, Ly LC, Horton JR, Li F, Quinlan KGR, Crossley M, Shi Y, Cheng X. Structural basis for human ZBTB7A action at the fetal globin promoter. Cell Rep 36(13):109759, 2021. e-Pub 2021. PMID: 34592153.
- 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.
- Curti BD, Koguchi Y, Leidner RS, Rolig AS, Sturgill ER, Sun Z, Wu Y, Rajamanickam V, Bernard B, Hilgart-Martiszus I, Fountain CB, Morris G, Iwamoto N, Shimada T, Chang S, Traber PG, Zomer E, Horton JR, Shlevin H, Redmond WL. Enhancing clinical and immunological effects of anti-PD-1 with belapectin, a galectin-3 inhibitor. J Immunother Cancer 9(4), 2021. e-Pub 2021. PMID: 33837055.
- Lan X, Ren R, Feng R, Ly LC, Lan Y, Zhang Z, Aboreden N, Qin K, Horton JR, Grevet JD, Mayuranathan T, Abdulmalik O, Keller CA, Giardine B, Hardison RC, Crossley M, Weiss MJ, Cheng X, Shi J, Blobel GA. ZNF410 Uniquely Activates the NuRD Component CHD4 to Silence Fetal Hemoglobin Expression. Mol Cell 81(2):239-254.e8, 2021. e-Pub 2021. PMID: 33301730.
- 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.
- 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. e-Pub 2020. PMID: 32453412.
- 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.
- 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 48(3):1466-1478, 2020. e-Pub 2020. PMID: 31879785.
- Wu X, Liu S, Sagum C, Chen J, Singh R, Chaturvedi A, Horton JR, Kashyap TR, Fushman D, Cheng X, Bedford MT, Wang B. Crosstalk between Lys63- and Lys11-polyubiquitin signaling at DNA damage sites is driven by Cezanne. Genes Dev 33(23-24):1702-1717, 2019. e-Pub 2019. PMID: 31699778.
- 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.
- Zoeller EL, Pedro B, Konen J, Dwivedi B, Rupji M, Sundararaman N, Wang L, Horton JR, Zhong C, Barwick BG, Cheng X, Martinez ED, Torres MP, Kowalski J, Marcus AI, Vertino PM. Genetic heterogeneity within collective invasion packs drives leader and follower cell phenotypes. J Cell Sci 132(19), 2019. e-Pub 2019. PMID: 31515279.
- 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.
- Milite C, Feoli A, Horton JR, Rescigno D, Cipriano A, Pisapia V, Viviano M, Pepe G, Amendola G, Novellino E, Cosconati S, Cheng X, Castellano S, Sbardella G. Discovery of a Novel Chemotype of Histone Lysine Methyltransferase EHMT1/2 (GLP/G9a) Inhibitors: Rational Design, Synthesis, Biological Evaluation, and Co-crystal Structure. J Med Chem 62(5):2666-2689, 2019. e-Pub 2019. PMID: 30753076.
- 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.
- 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.
- Ren R, Horton JR, Zhang X, Blumenthal RM, Cheng X. Detecting and interpreting DNA methylation marks. Curr Opin Struct Biol 53:88-99, 2018. e-Pub 2018. PMID: 30031306.
- Wu L, Cao J, Cai WL, Lang SM, Horton JR, Jansen DJ, Liu ZZ, Chen JF, Zhang M, Mott BT, Pohida K, Rai G, Kales SC, Henderson MJ, Hu X, Jadhav A, Maloney DJ, Simeonov A, Zhu S, Iwasaki A, Hall MD, Cheng X, Shadel GS, Yan Q. KDM5 histone demethylases repress immune response via suppression of STING. PLoS Biol 16(8):e2006134, 2018. e-Pub 2018. PMID: 30080846.
- 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.
- 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.
- 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.
- Horton JR, Liu X, Gale M, Wu L, Shanks JR, Zhang X, Webber PJ, Bell JS, 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):769-81, 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.
- Zhu XC, Sarker R, Horton JR, Chakraborty M, Chen TE, Tse CM, Cha B, Donowitz M. Nonsynonymous single nucleotide polymorphisms of NHE3 differentially decrease NHE3 transporter activity. Am J Physiol Cell Physiol 308(9):C758-66, 2015. e-Pub 2015. PMID: 25715704.
- 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.
- Daugherty AB, Horton JR, Cheng X, Lutz S. STRUCTURAL AND FUNCTIONAL CONSEQUENCES OF CIRCULAR PERMUTATION ON THE ACTIVE SITE OF OLD YELLOW ENZYME. ACS Catal 5(2):892-899, 2015. e-Pub 2015. PMID: 25692074.
Book Chapters
- Horton JR, Gale M, Yan Q, Cheng X. The Molecular Basis of Histone Demethylation. In: DNA and Histone Methylation as Cancer Targets. Humana Press, p. 151-219, 2017.
Grant & Contract Support
| Date: | 2024 - 2029 |
| Title: | A Functional Analysis of Arginine Methylation |
| Funding Source: | NIH |
| Role: | Co-I |
| ID: | R35GM153387-01 |
| Date: | 2023 - 2028 |
| Title: | Mechanisms of action and therapeutic targeting of the CARM1-NFIB axis in small cell lung cancer |
| Funding Source: | NIH/NCI |
| Role: | Co-I |
| ID: | R01CA272843-01A1 |
| Date: | 2020 - 2024 |
| Title: | Epigenetic regulations of DNA and histone methylation and demethylation: Structures and Mechanisms |
| Funding Source: | NIH |
| Role: | Co-I |
| ID: | R35GM134744 |
Patient Reviews
CV information above last modified February 27, 2025