title: Functional interaction among thyroid-specific transcription factors: Pax8 regulates the activity of Hex promoter.
abstract: The transcription factor Hex is expressed in the thyroid follicular cells (TFC) and in several other cell types. In TFC, Hex contributes to the control of the tissue-specific gene expression. By means of RT-PCR assays we found a correlation between the Hex and Pax8 (a different tissue-specific transcription factor, expressed in TFC) mRNA levels in normal and neoplastic thyroid tissues. This finding suggested the presence of a functional correlation between the two transcription factors. Therefore, we tested whether Pax8 regulates the transcriptional activity of Hex promoter. Indeed, by using cotransfection experiments in non-thyroidal cells, we show that increasing doses of Pax8 expression vector elicited a dose-dependent increase of the transcriptional activity of Hex promoter. Accordingly, gel-retardation assays indicated that in the Hex promoter are present several Pax8 binding sites. The Pax8 activating effect on Hex promoter was further increased by the contemporary presence of Hex protein. In fact, cotransfection of both Hex and Pax8 expression vectors doubled the transcriptional activity of Hex promoter with respect to the condition in which the Pax8 expression vector only was transfected. In addition, we show that also the transcriptional cofactor APE/Ref-1 cooperated with Pax8 for upregulation of Hex promoter activity. These findings, together with other published data, suggest that a network of functional interactions between transcriptional regulators is present in TFC.
authors.affiliation: Dipartimento di Scienze e Tecnologie Biomediche, Università di Udine, Piazzale Kolbe 1, 33100 Udine, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Puppin
authors.forename: Ivan
authors.initials: I
authors.lastname: Presta
authors.forename: Angela V
authors.initials: AV
authors.lastname: D'Elia
authors.forename: Gianluca
authors.initials: G
authors.lastname: Tell
authors.forename: Franco
authors.initials: F
authors.lastname: Arturi
authors.forename: Diego
authors.initials: D
authors.lastname: Russo
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Filetti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Damante
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D024202:Electrophoretic Mobility Shift Assay; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D009928:Organ Specificity; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; D011401:Promoter Regions, Genetic / Q000235:genetics*; D023302:Protein Footprinting; D012333:RNA, Messenger / Q000032:analysis; D013964:Thyroid Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D004268:DNA-Binding Proteins; C078492:HHEX protein, human; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors