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Identification of NIS and Duox2 as direct FoxE1 target genes in thyroid cells

AutorFernández, Lara P.; López-Márquez, Arístides ; Martínez, Ángel M.; Gómez-López, Gonzalo; Santisteban, Pilar
Fecha de publicación2013
CitaciónETA 2013
ResumenFoxE1, formerly known as Ttf2, is a thyroid-specific transcription factor belonging to the forkhead family which is able to interact with nucleosomes altering chromatin structure. This intrinsic property defines FoxE1 as a pioneer transcription factor essential during thyroid development, as well as for the maintenance of differentiated state in adults. Nevertheless, despite its importance, FoxE1 binding to DNA sequences other than the Tg and Tpo promoters remains almost unexplored. The aim of this work was to identify new FoxE1 downstream targets in thyroid follicular cells. We performed a genome-wide screening using expression arrays in FoxE1 knock-down PCCl3 cells, obtaining a set of genes regulated by FoxE1. To identify direct FoxE1 targets, we searched its core binding sequence, AAACA, in the promoters of regulated genes. As this sequence is easily found at random in the genome, we look for FoxE1 binding sites in close proximity (5–20 bp) to the NF1/CTF binding motif, as previously described for other forkhead factors. Experimental validation was done by RT-PCR, Western-blot, Chromatin immunoprecipitation (ChIp), Re-ChIP, and transfection assays. After FoxE1 silencing, we confirmed the decrease of its previously described target genes Tg and Tpo and interestingly, we also observed dowregulation of Nis and upregulation of Duox2. Functional analyzes showed specific in vivo FoxE1 binding to novel regulatory regions of both Duox2 and NIS genes. Moreover, we demonstrated simultaneous binding of FoxE1 and NF1/CTF to the Nis upstream enhancer region, as well as a clear functional activation of the Nis promoter by both transcription factors. In conclusion our data show the implication of Nis and Duox2 in executing the transcriptional program triggered by FoxE1.
DescripciónResumen del trabajo presentado al 37th Annual Meeting of the European Thyroid Association, celebrado en Leiden (Holanda) del 7 al 11 de septiembre de 2013.
Aparece en las colecciones: (IIBM) Comunicaciones congresos
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