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A novel allosteric mechanism on protein-DNA interactions underlying the phosphorylation-dependent regulation of Ets1 target gene expressions.

Shiina M, Hamada K, Inoue-Bungo T, Shimamura M, Uchiyama A, Baba S, Sato K, Yamamoto M, Ogata K
J Mol Biol 427 1655-69 (2015)
Related entries: 3wts, 3wtt, 3wtu, 3wtw, 3wtx, 3wty, 3wtz, 3wu0, 3wu1

Cited: 18 times
EuropePMC logo PMID: 25083921

Abstract

Cooperative assemblies of transcription factors (TFs) on target gene enhancers coordinate cell proliferation, fate specification, and differentiation through precise and complicated transcriptional mechanisms. Chemical modifications, such as phosphorylation, of TFs induced by cell signaling further modulate the dynamic cooperativity of TFs. In this study, we found that various Ets1-containing TF-DNA complexes respond differently to calcium-induced phosphorylation of Ets1, which is known to inhibit Ets1-DNA binding. Crystallographic analysis of a complex comprising Ets1, Runx1, and CBFβ at the TCRα enhancer revealed that Ets1 acquires robust binding stability in the Runx1 and DNA-complexed state, via allosteric mechanisms. This allows phosphorylated Ets1 to be retained at the TCRα enhancer with Runx1, in contrast to other Ets1 target gene enhancers including mb-1 and stromelysin-1. This study provides a structure-based model for cell-signaling-dependent regulation of target genes, mediated via chemical modification of TFs.

Articles - 3wtv mentioned but not cited (1)

  1. PNImodeler: web server for inferring protein-binding nucleotides from sequence data. Im J, Tuvshinjargal N, Park B, Lee W, Huang DS, Han K. BMC Genomics 16 Suppl 3 S6 (2015)


Reviews citing this publication (1)

  1. Studies on Molecular Dynamics of Intrinsically Disordered Proteins and Their Fuzzy Complexes: A Mini-Review. Kasahara K, Terazawa H, Takahashi T, Higo J. Comput Struct Biotechnol J 17 712-720 (2019)

Articles citing this publication (16)

  1. Identification of Human Lineage-Specific Transcriptional Coregulators Enabled by a Glossary of Binding Modules and Tunable Genomic Backgrounds. Mariani L, Weinand K, Vedenko A, Barrera LA, Bulyk ML. Cell Syst 5 187-201.e7 (2017)
  2. Structured and disordered regions cooperatively mediate DNA-binding autoinhibition of ETS factors ETV1, ETV4 and ETV5. Currie SL, Lau DKW, Doane JJ, Whitby FG, Okon M, McIntosh LP, Graves BJ. Nucleic Acids Res 45 2223-2241 (2017)
  3. Phosphorylation of an intrinsically disordered region of Ets1 shifts a multi-modal interaction ensemble to an auto-inhibitory state. Kasahara K, Shiina M, Higo J, Ogata K, Nakamura H. Nucleic Acids Res 46 2243-2251 (2018)
  4. Allosterism and signal transfer in DNA. Balaceanu A, Pérez A, Dans PD, Orozco M. Nucleic Acids Res 46 7554-7565 (2018)
  5. Conformational Dynamics and the Binding of Specific and Nonspecific DNA by the Autoinhibited Transcription Factor Ets-1. Desjardins G, Okon M, Graves BJ, McIntosh LP. Biochemistry 55 4105-4118 (2016)
  6. Electrostatic repulsion causes anticooperative DNA binding between tumor suppressor ETS transcription factors and JUN-FOS at composite DNA sites. Madison BJ, Clark KA, Bhachech N, Hollenhorst PC, Graves BJ, Currie SL. J Biol Chem 293 18624-18635 (2018)
  7. Autoinhibition of ETV6 DNA Binding Is Established by the Stability of Its Inhibitory Helix. De S, Okon M, Graves BJ, McIntosh LP. J Mol Biol 428 1515-1530 (2016)
  8. Molecular mechanisms of cooperative binding of transcription factors Runx1-CBFβ-Ets1 on the TCRα gene enhancer. Kasahara K, Shiina M, Fukuda I, Ogata K, Nakamura H. PLoS One 12 e0172654 (2017)
  9. Allosteric interference in oncogenic FLI1 and ERG transactions by mithramycins. Hou C, Mandal A, Rohr J, Tsodikov OV. Structure 29 404-412.e4 (2021)
  10. Biochemical and structural characterization of a novel cooperative binding mode by Pit-1 with CATT repeats in the macrophage migration inhibitory factor promoter. Agarwal S, Cho TY. Nucleic Acids Res 46 929-941 (2018)
  11. Computational characterization of the binding mode between oncoprotein Ets-1 and DNA-repair enzymes. de Ruyck J, Brysbaert G, Villeret V, Aumercier M, Lensink MF. Proteins 86 1055-1063 (2018)
  12. New insights into transcriptional and leukemogenic mechanisms of AML1-ETO and E2A fusion proteins. Li J, Guo C, Steinauer N, Zhang J. Front Biol (Beijing) 11 285-304 (2016)
  13. Ultrafast differential flexibility of Cro-protein binding domains of two operator DNAs with different sequences. Choudhury S, Ghosh B, Singh P, Ghosh R, Roy S, Pal SK. Phys Chem Chem Phys 18 17983-17990 (2016)
  14. In-silico probing of AML related RUNX1 cancer-associated missense mutations: Predicted relationships to DNA binding and drug interactions. Ullah H, Zhang B, Sharma NK, McCrea PD, Srivastava Y. Front Mol Biosci 9 981020 (2022)
  15. Alprazolam Prompts HIV-1 Transcriptional Reactivation and Enhances CTL Response Through RUNX1 Inhibition and STAT5 Activation. Lin A, Elbezanti WO, Schirling A, Ahmed A, Van Duyne R, Cocklin S, Klase Z. Front Neurol 12 663793 (2021)
  16. High-throughput data and modeling reveal insights into the mechanisms of cooperative DNA-binding by transcription factor proteins. Martin V, Zhuang F, Zhang Y, Pinheiro K, Gordân R. Nucleic Acids Res 51 11600-11612 (2023)


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