Skip to main content
Log in

GATA4 inhibits expression of the tryptophan oxygenase gene by binding to the TATA box in fetal hepatocytes

  • JAACT Special Issue
  • Published:
Cytotechnology Aims and scope Submit manuscript

Abstract

The glucocorticoid receptor regulates liver-specific expression of the tryptophan oxygenase gene through glucocorticoid responsive elements located −0.45 and −1.2 kb from the transcription start site. However, the hormone-mediated induction is restricted to adult hepatocytes, and fetal hepatocytes are unable to express the gene even in the presence of the receptor and glucocorticoid hormone. The difference in sensitivity to the hormone between adult and fetal hepatocytes has not been well understood. In this study, we analyzed the structure of the tryptophan oxygenase gene’s promoter. The promoter has two TATA boxes, and transcription starts from the downstream TATA box. We found that a transcription factor GATA4 bound to the downstream TATA box and may inhibit the binding of TATA-binding protein, resulting in transcriptional repression even in the presence of glucocorticoid in fetal hepatocytes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Bresnick EH, Martowicz ML, Pal S, Johnson KD (2005) Developmental control via GATA factor interplay at chromatin domains. J Cell Physiol 205:1–9

    Article  CAS  Google Scholar 

  • Chen GY, Osada H, Santamaria-Babi LF, Kannagi R (2006) Interaction of GATA-3/T-bet transcription factors regulates expression of sialyl Lewis X homing receptors on Th1/Th2 lymphocytes. Proc Natl Acad Sci USA 103:16894–16899

    Article  CAS  Google Scholar 

  • Dohda T, Kaneoka H, Inayoshi Y, Kamihira M, Miyake K, Iijima S (2004) Transcriptional coactivators CBP and p300 cooperatively enhance HNF-1α-mediated expression of the albumin gene in hepatocytes. J Biochem 136:313–319

    Article  CAS  Google Scholar 

  • Danesch U, Gloss B, Schmid W, Schütz G, Schüle R, Renkawitz R (1987) Glucocorticoid induction of the rat tryptophan oxygenase gene is mediated by two widely separated glucocorticoid-responsive elements. EMBO J 6:625–630

    CAS  Google Scholar 

  • Hebbar PB, Archer TK (2003) Chromatin remodeling by nuclear receptors. Chromosoma 111:495–504

    Article  Google Scholar 

  • Inayoshi Y, Kaneoka H, Machida Y, Terajima M, Dohda T, Miyake K, Iijima S (2005) Repression of GR-mediated expression of the tryptophan oxygenase gene by the SWI/SNF complex during liver development. J Biochem 138:457–465

    Article  CAS  Google Scholar 

  • Kumar MV, Tindall DJ (1998) Transcriptional regulation of the steroid receptor genes. Prog Nucleic Acid Res Mol Biol 59:289–306

    Article  CAS  Google Scholar 

  • Nakamura T, Shinno H, Ichihara A (1980) Insulin and glucagons as a new regulator system for tryptophan oxygenase activity demonstrated in primary cultured rat hepatocytes. J Biol Chem 255:7533–7535

    CAS  Google Scholar 

  • Nakamura T, Niimi S, Nawa K, Noda C, Ichihara A, Takagi Y, Anai M, Sakaki Y (1987) Multihormonal regulation of transcription of the tryptophan 2,3-dixygenase gene in primary cultures of adult rat hepatocytes with special reference to the presence of a transcriptional protein mediating the actin of glucocorticoids. J Biol Chem 262:727–733

    CAS  Google Scholar 

  • Patient RK, McGhee JD (2002) The GATA family (vertebrates and invertebrates). Curr Opin Genet Dev 12:416–422

    Article  CAS  Google Scholar 

  • Schmid W, Scherer G, Danesch U, Zentgraf H, Matthias P, Strange CM, Röwekamp W, Schutz G (1982) Isolation and characterization of the rat tryptophan oxygenase gene. EMBO J 1:1287–1293

    CAS  Google Scholar 

  • Svensson EC, Huggins GS, Dardik FB, Polk CE, Leiden JM (2000) A functionally conserved N-terminal domain of the friend of GATA-2 (FOG-2) protein represses GATA4-dependent transcription. J Biol Chem 275:20762–20769

    Article  CAS  Google Scholar 

  • Watt AJ, Zhao R, Li J, Duncan SA (2007) Development of the mammalian liver and ventral pancreas is dependent on GATA4. BMC Dev Biol 7. doi:10.1186/1471-213X-7-37

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Katsuhide Miyake.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kaneoka, H., Miyake, K. & Iijima, S. GATA4 inhibits expression of the tryptophan oxygenase gene by binding to the TATA box in fetal hepatocytes. Cytotechnology 57, 123–128 (2008). https://doi.org/10.1007/s10616-007-9120-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10616-007-9120-1

Keywords

Navigation