Multiple mechanisms of growth hormone-regulated gene transcription

Teresa I. Ceseña, Tracy Xiao Cui, Graciela Piwien-Pilipuk, Julianne Kaplani, Anda Alexandra Calinescu, Jeffrey S. Huo, Jorge A. Iñiguez-Lluhí, Roland Kwok, Jessica Schwartz

Research output: Contribution to journalReview article

Abstract

Diverse physiological actions of growth hormone (GH) are mediated by changes in gene transcription. Transcription can be regulated at several levels, including post-translational modification of transcription factors, and formation of multiprotein complexes involving transcription factors, co-regulators and additional nuclear proteins; these serve as targets for regulation by hormones and signaling pathways. Evidence that GH regulates transcription at multiple levels is exemplified by analysis of the proto-oncogene c-fos. Among the GH-regulated transcription factors on c-fos, C/EBPβ appears to be key, since depletion of C/EBPβ by RNA interference blocks the stimulation of c-fos by GH. The phosphorylation state of C/EBPβ and its ability to activate transcription are regulated by GH through MAPK and PI3K/Akt-mediated signaling cascades. The acetylation of C/EBPβ also contributes to its ability to activate c-fos transcription. These and other post-translational modifications of C/EBPβ appear to be integrated for regulation of transcription by GH. The formation of nuclear proteins into complexes associated with DNA-bound transcription factors is also regulated by GH. Both C/EBPβ and the co-activator p300 are recruited to c-fos in response to GH, altering c-fos promoter activation. In addition, GH rapidly induces spatio-temporal re-localization of C/EBPβ within the nucleus. Thus, GH-regulated gene transcription mediated by C/EBPβ reflects the integration of diverse mechanisms including post-translational modifications, modulation of protein complexes associated with DNA and re-localization of gene regulatory proteins. Similar integration involving other transcription factors, including Stats, appears to be a feature of regulation by GH of other gene targets.

Original languageEnglish (US)
Pages (from-to)126-133
Number of pages8
JournalMolecular genetics and metabolism
Volume90
Issue number2
DOIs
StatePublished - Feb 1 2007

Keywords

  • Acetylation
  • C/EBPβ
  • Co-activator complex
  • Heterochromatin
  • Phosphorylation
  • Stats
  • c-fos
  • p300

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology

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  • Cite this

    Ceseña, T. I., Cui, T. X., Piwien-Pilipuk, G., Kaplani, J., Calinescu, A. A., Huo, J. S., Iñiguez-Lluhí, J. A., Kwok, R., & Schwartz, J. (2007). Multiple mechanisms of growth hormone-regulated gene transcription. Molecular genetics and metabolism, 90(2), 126-133. https://doi.org/10.1016/j.ymgme.2006.10.006