ArticleBMC genomics2010
Comparative genomics reveals a functional thyroid-specific element in the far upstream region of the PAX8 gene.
Article in BMC genomics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 23 citations in OpenAlex.
- A case report of ectopic thyroid adenoma resection by transaxillary non-inflatable endoscopic surgery.International journal of surgery case reports · 2024Article
- GLIS3 regulates transcription of thyroid hormone biosynthetic genes in coordination with other thyroid transcription factors.Cell & bioscience · 2023Article
- Hepatic incidentaloma: An asymptomatic ectopic thyroid tissue.Frontiers in endocrinology · 2022Article
- Papillary Thyroid Carcinoma Cervical Lymph Node Metastasis with Cystic Change Differentiated from Congenital Cystic Lesions with the Assistance of Immunohistochemistry: A Case Study.Head and neck pathology · 2017Article
- The diagnostic utility of the triple markers Napsin A, TTF-1, and PAX8 in differentiating between primary and metastatic lung carcinomas.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Novel loci associated with usual sleep duration: the CHARGE Consortium Genome-Wide Association Study.Molecular psychiatry · 2015Article
- Synergistic signaling of KRAS and thyroid hormone receptor β mutants promotes undifferentiated thyroid cancer through MYC up-regulation.Neoplasia (New York, N.Y.) · 2014Article
- An essential role for Pax8 in the transcriptional regulation of cadherin-16 in thyroid cells.Molecular endocrinology (Baltimore, Md.) · 2012Article
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Authors and funding
8 authors at 4 institutions in 1 country.
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Abstract
backgroundThe 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.
resultsWe 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.
conclusionsResults 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.
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