HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Comparative genomics reveals a functional thyroid-specific element in the far upstream region of the PAX8 gene.

AbstractBACKGROUND:
The molecular mechanisms leading to a fully differentiated thyrocite are still object of intense study even if it is well known that thyroglobulin, thyroperoxidase, NIS and TSHr are the marker genes of thyroid differentiation. It is also well known that Pax8, TTF-1, Foxe1 and Hhex are the thyroid-enriched transcription factors responsible for the expression of the above genes, thus are responsible for the differentiated thyroid phenotype. In particular, the role of Pax8 in the fully developed thyroid gland was studied in depth and it was established that it plays a key role in thyroid development and differentiation. However, to date the bases for the thyroid-enriched expression of this transcription factor have not been unraveled yet. Here, we report the identification and characterization of a functional thyroid-specific enhancer element located far upstream of the Pax8 gene.
RESULTS:
We hypothesized that regulatory cis-acting elements are conserved among mammalian genes. Comparison of a genomic region extending for about 100 kb at the 5'-flanking region of the mouse and human Pax8 gene revealed several conserved regions that were tested for enhancer activity in thyroid and non-thyroid cells. Using this approach we identified one putative thyroid-specific regulatory element located 84.6 kb upstream of the Pax8 transcription start site. The in silico data were verified by promoter-reporter assays in thyroid and non-thyroid cells. Interestingly, the identified far upstream element manifested a very high transcriptional activity in the thyroid cell line PC Cl3, but showed no activity in HeLa cells. In addition, the data here reported indicate that the thyroid-enriched transcription factor TTF-1 is able to bind in vitro and in vivo the Pax8 far upstream element, and is capable to activate transcription from it.
CONCLUSIONS:
Results of this study reveal the presence of a thyroid-specific regulatory element in the 5' upstream region of the Pax8 gene. The identification of this regulatory element represents the first step in the investigation of upstream regulatory mechanisms that control Pax8 transcription during thyroid differentiation and are relevant to further studies on Pax8 as a candidate gene for thyroid dysgenesis.
AuthorsRoberto Nitsch, Valeria Di Dato, Alessandra di Gennaro, Tiziana de Cristofaro, Serena Abbondante, Mario De Felice, Mariastella Zannini, Roberto Di Lauro
JournalBMC genomics (BMC Genomics) Vol. 11 Pg. 306 (May 14 2010) ISSN: 1471-2164 [Electronic] England
PMID20470391 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • DNA-Binding Proteins
  • PAX8 Transcription Factor
  • PAX8 protein, human
  • Paired Box Transcription Factors
  • Pax8 protein, mouse
  • TTF1 protein, human
  • Transcription Factors
  • Ttf1 protein, mouse
Topics
  • 5' Flanking Region (genetics)
  • Animals
  • Conserved Sequence
  • DNA-Binding Proteins (metabolism)
  • Enhancer Elements, Genetic (genetics)
  • Gene Expression Regulation
  • Genomics
  • Humans
  • Mice
  • Organ Specificity
  • PAX8 Transcription Factor
  • Paired Box Transcription Factors (genetics, metabolism)
  • Phylogeny
  • Sequence Alignment
  • Sequence Homology, Nucleic Acid
  • Thyroid Gland (cytology, metabolism)
  • Transcription Factors
  • Transcription, Genetic

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: