Tissue-specific transcriptional regulation is achieved by the combined action of transcription factors, co-regulators and components of the basal transcriptional machinery. The goal of our work is to unravel the mechanisms involved in the regulation of the activity of thyroid-specific transcription factors. We have demonstrated that the transcription factor Pax8 is required for the expression of all the thyroid-specific genes that are considered markers of the differentiated phenotype of this cell type. Moreover, we have recently shown that Pax8 biochemically interacts with TTF-1, another transcription factor involved in thyroid gene expression. Interestingly, the physical interaction between the two factors leads to a strong synergistic effect on the transcriptional activation of a thyroid-specific gene promoter. Although Pax8 and TTF-1 influence the expression of various genes during mouse embryonic development, their mode of action as transcription factors remain poorly understood.
TAZ is a transcriptional coactivator that regulates the activity of several transcription factors therefore playing a central role in tissue-specific transcription. The recently demonstrated physical and functional interaction between TAZ and TTF-1 in the lung raised the question of whether TAZ could be an important regulatory molecule also in the thyroid. In our study, we demonstrated the presence of TAZ in thyroid cells and the existence of an important cooperation between TAZ and the transcription factors Pax8 and TTF-1 in the modulation of thyroid gene expression. In addition, we revealed that the three proteins are co-expressed in the nucleus of differentiated thyroid cells and that TAZ interacts with both Pax8 and TTF-1, in vitro and in vivo. More importantly, we show that this interaction leads to a significant enhancement of the transcriptional activity of Pax8 and TTF-1 on the thyroglobulin promoter thus suggesting a fundamental role of TAZ in the control of genes involved in thyroid development and differentiation.
03 - 07 May 2008
European Society of Endocrinology