Back to Search
Start Over
Comparative genomics reveals a functional thyroid-specific element in the far upstream region of the PAX8 gene
- Source :
- BMC Genomics, BMC genomics 11 (2010): 306-1–306-13., info:cnr-pdr/source/autori:Nitsch R, Di Dato V, di Gennaro A, de Cristofaro T, Abbondante S, De Felice M, Zannini M, Di Lauro R./titolo:Comparative genomics reveals a functional thyroid-specific element in the far upstream region of the PAX8 gene./doi:/rivista:BMC genomics/anno:2010/pagina_da:306-1/pagina_a:306-13/intervallo_pagine:306-1–306-13/volume:11, BMC Genomics, Vol 11, Iss 1, p 306 (2010)
- Publication Year :
- 2010
- Publisher :
- Springer Science and Business Media LLC, 2010.
-
Abstract
- Background 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.
- Subjects :
- Transcription, Genetic
endocrine system diseases
PROMOTER
5' Flanking Region
medicine.medical_treatment
Thyroid Gland
Mice
0302 clinical medicine
Paired Box Transcription Factors
TRANSCRIPTION FACTOR
Conserved Sequence
Phylogeny
Genetics
Regulation of gene expression
0303 health sciences
biology
HOMEODOMAIN
Genomics
DNA-Binding Proteins
DIFFERENTIATION
Enhancer Elements, Genetic
Organ Specificity
030220 oncology & carcinogenesis
RECEPTOR ACTIVATOR
Research Article
Biotechnology
endocrine system
lcsh:QH426-470
lcsh:Biotechnology
5' flanking region
BAC DNA
ENHANCER
PAX8 Transcription Factor
03 medical and health sciences
Thyroid peroxidase
lcsh:TP248.13-248.65
Sequence Homology, Nucleic Acid
medicine
Animals
Humans
Enhancer
Transcription factor
030304 developmental biology
RECOGNITION
lcsh:Genetics
Gene Expression Regulation
CELLS
biology.protein
Thyroglobulin
PAX8
Sequence Alignment
TISSUE-SPECIFIC EXPRESSION
Transcription Factors
FOXE1
Subjects
Details
- ISSN :
- 14712164
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- BMC Genomics
- Accession number :
- edsair.doi.dedup.....66c6362cba4385c73f92450c96385aa5