• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of biochemjBJ Latest papers and much more!
Biochem J. Apr 1, 1998; 331(Pt 1): 37–40.
PMCID: PMC1219318

PAX 8 activates the enhancer of the human thyroperoxidase gene.


In this study we report on a novel natural target of the paired domain transcription factor PAX 8 in the enhancer element of the human thyroperoxidase gene, one of the most important thyroid differentiation markers. It is the primary enzyme involved in thyroid hormone synthesis and PAX 8 has been previously identified as an activating factor of the rat thyroperoxidase gene promoter. In vitro, PAX 8 binds a cis element of the human enhancer and its exogenous expression induces the enhancer activity in co-transfection experiments in Cos-7 cells. When mutated at this binding site, the enhancer is no longer activated by PAX 8. Our finding strengthens the PAX 8 role in the maintenance of thyroid differentiation and in particular in the tissue-specific thyroperoxidase gene expression.

Full Text

The Full Text of this article is available as a PDF (239K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Damante G, Di Lauro R. Thyroid-specific gene expression. Biochim Biophys Acta. 1994 Aug 2;1218(3):255–266. [PubMed]
  • Francis-Lang H, Price M, Polycarpou-Schwarz M, Di Lauro R. Cell-type-specific expression of the rat thyroperoxidase promoter indicates common mechanisms for thyroid-specific gene expression. Mol Cell Biol. 1992 Feb;12(2):576–588. [PMC free article] [PubMed]
  • Abramowicz MJ, Vassart G, Christophe D. Functional study of the human thyroid peroxidase gene promoter. Eur J Biochem. 1992 Feb 1;203(3):467–473. [PubMed]
  • Foti D, Gestautas J, Rapoport B. Studies on the functional activity of the promoter for the human thyroid peroxidase gene. Biochem Biophys Res Commun. 1990 Apr 16;168(1):281–287. [PubMed]
  • Zannini M, Francis-Lang H, Plachov D, Di Lauro R. Pax-8, a paired domain-containing protein, binds to a sequence overlapping the recognition site of a homeodomain and activates transcription from two thyroid-specific promoters. Mol Cell Biol. 1992 Sep;12(9):4230–4241. [PMC free article] [PubMed]
  • Civitareale D, Lonigro R, Sinclair AJ, Di Lauro R. A thyroid-specific nuclear protein essential for tissue-specific expression of the thyroglobulin promoter. EMBO J. 1989 Sep;8(9):2537–2542. [PMC free article] [PubMed]
  • Kikkawa F, Gonzalez FJ, Kimura S. Characterization of a thyroid-specific enhancer located 5.5 kilobase pairs upstream of the human thyroid peroxidase gene. Mol Cell Biol. 1990 Dec;10(12):6216–6224. [PMC free article] [PubMed]
  • Mizuno K, Gonzalez FJ, Kimura S. Thyroid-specific enhancer-binding protein (T/EBP): cDNA cloning, functional characterization, and structural identity with thyroid transcription factor TTF-1. Mol Cell Biol. 1991 Oct;11(10):4927–4933. [PMC free article] [PubMed]
  • Ho SN, Hunt HD, Horton RM, Pullen JK, Pease LR. Site-directed mutagenesis by overlap extension using the polymerase chain reaction. Gene. 1989 Apr 15;77(1):51–59. [PubMed]
  • Plachov D, Chowdhury K, Walther C, Simon D, Guenet JL, Gruss P. Pax8, a murine paired box gene expressed in the developing excretory system and thyroid gland. Development. 1990 Oct;110(2):643–651. [PubMed]
  • Civitareale D, Castelli MP, Falasca P, Saiardi A. Thyroid transcription factor 1 activates the promoter of the thyrotropin receptor gene. Mol Endocrinol. 1993 Dec;7(12):1589–1595. [PubMed]
  • Shapiro DJ, Sharp PA, Wahli WW, Keller MJ. A high-efficiency HeLa cell nuclear transcription extract. DNA. 1988 Jan-Feb;7(1):47–55. [PubMed]
  • Hollon T, Yoshimura FK. Variation in enzymatic transient gene expression assays. Anal Biochem. 1989 Nov 1;182(2):411–418. [PubMed]
  • Czerny T, Schaffner G, Busslinger M. DNA sequence recognition by Pax proteins: bipartite structure of the paired domain and its binding site. Genes Dev. 1993 Oct;7(10):2048–2061. [PubMed]
  • Czerny T, Busslinger M. DNA-binding and transactivation properties of Pax-6: three amino acids in the paired domain are responsible for the different sequence recognition of Pax-6 and BSAP (Pax-5). Mol Cell Biol. 1995 May;15(5):2858–2871. [PMC free article] [PubMed]
  • Dörfler P, Busslinger M. C-terminal activating and inhibitory domains determine the transactivation potential of BSAP (Pax-5), Pax-2 and Pax-8. EMBO J. 1996 Apr 15;15(8):1971–1982. [PMC free article] [PubMed]
  • Noll M. Evolution and role of Pax genes. Curr Opin Genet Dev. 1993 Aug;3(4):595–605. [PubMed]
  • Dumont JE, Lamy F, Roger P, Maenhaut C. Physiological and pathological regulation of thyroid cell proliferation and differentiation by thyrotropin and other factors. Physiol Rev. 1992 Jul;72(3):667–697. [PubMed]
  • Gérard CM, Lefort A, Christophe D, Libert F, Van Sande J, Dumont JE, Vassart G. Control of thyroperoxidase and thyroglobulin transcription by cAMP: evidence for distinct regulatory mechanisms. Mol Endocrinol. 1989 Dec;3(12):2110–2118. [PubMed]
  • Santisteban P, Acebrón A, Polycarpou-Schwarz M, Di Lauro R. Insulin and insulin-like growth factor I regulate a thyroid-specific nuclear protein that binds to the thyroglobulin promoter. Mol Endocrinol. 1992 Aug;6(8):1310–1317. [PubMed]
  • Saito T, Endo T, Nakazato M, Kogai T, Onaya T. Thyroid-stimulating hormone-induced down-regulation of thyroid transcription factor 1 in rat thyroid FRTL-5 cells. Endocrinology. 1997 Feb;138(2):602–606. [PubMed]
  • Van Renterghem P, Vassart G, Christophe D. Pax 8 expression in primary cultured dog thyrocyte is increased by cyclic AMP. Biochim Biophys Acta. 1996 Jun 3;1307(1):97–103. [PubMed]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...