A Profile HMM for Recognition of Hormone Response Elements

  • Maria Stepanova
  • Feng Lin
  • Valerie C. -L. Lin
Conference paper
Part of the Lecture Notes in Computer Science book series (LNCS, volume 4146)


Steroid hormones are necessary for most vital functions of vertebrate organisms, and act within cells via interaction with their receptor molecules. Steroid hormone receptors are transcription factors. Identification of Hormone response elements (HREs) on DNA is essential for understanding the mechanism of gene regulation by steroid hormones. In this work we present a systematic approach for recognition of steroid HREs within promoters of vertebrate genomes, based on extensive experimental dataset and specifically reconstructed Profile Hidden Markov Model of putative HREs. The model can be trained for further prediction of HREs in promoters of hormone responsive genes, and therefore, investigation of direct targets for androgen, progesterone and glucocorticoid hormones. Additional documentation and supplementary data, as well as the web-based program developed for steroid HRE prediction are available at http://birc.ntu.edu.sg/~pmaria .


Hide Markov Model Steroid Hormone Receptor Estrogen Response Element Hormone Response Element Primary Target Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Conneely, O.M.: Perspective: Female Steroid Hormone Action. Endocrinology 142(6), 2194–2199 (2001)CrossRefGoogle Scholar
  2. 2.
    Eddy, E.M., Washburn, T.F., Bunch, D.O., Goulding, E.H., Gladen, B.C., Lubahn, D.B., Korach, K.S.: Targeted disruption of the estrogen receptor gene in male mice causes alteration of spermatogenesis and infertility. Endocrinology 137(11), 4796–4805 (1996)CrossRefGoogle Scholar
  3. 3.
    Pelzer, T., Shamim, A., Wolfges, S., Schumann, M., Neyses, L.: Modulation of cardiac hypertrophy by estrogens. Adv. Exp. Med. Biol. 432, 83–89 (1997)Google Scholar
  4. 4.
    Cutolo, M., Sulli, A., Capellino, S., Villaggio, B., Montagna, P., Seriolo, B., Straub, R.H.: Sex hormones influence on the immune system: basic and clinical aspects in autoimmunity. Lupus 13(9), 635–638 (2004)CrossRefGoogle Scholar
  5. 5.
    Maggi, A., Ciana, P., Belcredito, S., Vegeto, E.: Estrogens in the nervous system: mechanisms and nonreproductive functions. Annu. Rev. Physiol. 66, 291–313 (2004)CrossRefGoogle Scholar
  6. 6.
    Kearns, A.E., Khosla, S.: Potential anabolic effects of androgens on bone. Mayo Clin. Proc. 79(4S), 14–18 (2004)Google Scholar
  7. 7.
    Tsai, M.J., O’Malley, B.W.: Molecular mechanisms of action of steroid/thyroid receptor superfamily members. Annu. Rev. Biochem. 63, 451–486 (1994)CrossRefGoogle Scholar
  8. 8.
    Alberts, B., Bray, D., Lewis, J., Raff, M., Roberts, K., Watson, J.: Intercellular signalling. Molecular Biology of the Cell. Garland Publishing, New York (1994)Google Scholar
  9. 9.
    Dahlman-Wright, K., Siltala-Roos, H., Carlstedt-Duke, J., Gustafsson, J.A.: Protein-protein interactions facilitate DNA binding by the glucocorticoid receptor DNA-binding domain. J. Biol. Chem. 265(23), 14030–14035 (1990)Google Scholar
  10. 10.
    Bajic, V.B., Tan, S.L., Chong, A., Tang, S., Strom, A., Gustafsson, J.A., Lin, C.Y., Liu, E.T.: Dragon ERE Finder version 2: A tool for accurate detection and analysis of estrogen response elements in vertebrate genomes. Nucleic Acids Res. 31(13), 3605–3607 (2003)CrossRefGoogle Scholar
  11. 11.
    Barbulescu, K., Geserick, C., Schuttke, I., Schleuning, W.D., Haendler, B.: New androgen response elements in the murine pem promoter mediate selective transactivation. Mol. Endocrinol. 15(10), 1803–1816 (2001)CrossRefGoogle Scholar
  12. 12.
    Truss, M., Chalepakis, G., Beato, M.: Contacts between steroid hormone receptors and thymines in DNA: an interference method. Proc. Natl. Acad. Sci. USA 87(18), 7180–7184 (1990)CrossRefGoogle Scholar
  13. 13.
    Evans, R.M.: The steroid and thyroid hormone receptor superfamily. Science 240(4854), 889–895 (1988)CrossRefGoogle Scholar
  14. 14.
    Wasserman, W.W., Sandelin, A.: Applied bioinformatics for the identification of regulatory elements. Nat. Rev. Genet. 5(4), 276–287 (2004)CrossRefGoogle Scholar
  15. 15.
    Favorov, A.V., Gelfand, M.S., Gerasimova, A.V., Ravcheev, D.A., Mironov, A.A., Makeev, V.J.: A Gibbs sampler for identification of symmetrically structured, spaced DNA motifs with improved estimation of the signal length. Bioinformatics 21(10), 2240–2245 (2005)CrossRefGoogle Scholar
  16. 16.
    Sandelin, A., Wasserman, W.W.: Prediction of nuclear hormone receptor response elements. Mol. Endocrinol. 19(3), 595–606 (2005)CrossRefGoogle Scholar
  17. 17.
    Bono, H.U.: SayaMatcher: Genome scale organization and systematic analysis of nuclear receptor response elements. Gene. 364, 74–78 (2005)CrossRefGoogle Scholar
  18. 18.
    Eddy, S.R.: Profile hidden Markov models. Bioinformatics 14(9), 755–763 (1998)CrossRefGoogle Scholar
  19. 19.
    Vega, V.B., Bangarusamy, D.K., Miller, L.D., Liu, E.T., Lin, C.Y.: BEARR: Batch Extraction and Analysis of cis-Regulatory Regions. Nucleic Acids Res. 32(Web Server Issue), 257–260 (2004)CrossRefGoogle Scholar
  20. 20.
    Leo, J.C., Wang, S.M., Guo, C.H., Aw, S.E., Zhao, Y., Li, J.M., Hui, K.M., Lin, V.C.: Gene regulation profile reveals consistent anticancer properties of progesterone in hormone-independent breast cancer cells transfected with progesterone receptor. Int. J. Cancer 117(4), 561–568 (2005)CrossRefGoogle Scholar
  21. 21.
    Tsai, S.Y., Tsai, M.J., O’Malley, B.W.: Cooperative binding of steroid hormone receptors contributes to transcriptional synergism at target enhancer elements. Cell. 57(3), 443–448 (1989)CrossRefGoogle Scholar
  22. 22.
    Lapp, C.A., Lohse, J.E., Lewis, J.B., Dickinson, D.P., Billman, M., Hanes, P.J., Lapp, D.F.: The effects of progesterone on matrix metalloproteinases in cultured human gingival fibroblasts. J. Periodontol. 74(3), 277–288 (2003)CrossRefGoogle Scholar
  23. 23.
    Bjorling, D.E., Beckman, M., Clayton, M.K., Wang, Z.Y.: Modulation of nerve growth factor in peripheral organs by estrogen and progesterone. Neuroscience 110(1), 155–167 (2002)CrossRefGoogle Scholar
  24. 24.
    Hoffmann, E., Thiefes, A., Buhrow, D., Dittrich-Breiholz, O., Schneider, H., Resch, K., Kracht, M.: MEK1-dependent delayed expression of Fos-related antigen-1 counteracts c-Fos and p65 NF-kappaB-mediated interleukin-8 transcription in response to cytokines or growth factors. J. Biol. Chem. 280(10), 9706–9718 (2005)CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2006

Authors and Affiliations

  • Maria Stepanova
    • 1
  • Feng Lin
    • 2
  • Valerie C. -L. Lin
    • 3
  1. 1.Bioinformatics Research CentreNanyang Technological UniversitySingapore
  2. 2.School of Computer EngineeringNanyang Technological UniversitySingapore
  3. 3.School of Biological SciencesNanyang Technological UniversitySingapore

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