In this study we report on a novel natural target of the paired domain transcription factor PAX 8 in the enhancer element of the human thyroperoxidase gene, one of the most important thyroid differentiation markers. It is the primary enzyme involved in thyroid hormone synthesis and PAX 8 has been previously identified as an activating factor of the rat thyroperoxidase gene promoter. In vitro, PAX 8 binds a ciselement of the human enhancer and its exogenous expression induces the enhancer activity in co-transfection experiments in Cos-7 cells. When mutated at this binding site, the enhancer is no longer activated by PAX 8. Our finding strengthens the PAX 8 role in the maintenance of thyroid differentiation and in particular in the tissue-specific thyroperoxidase gene expression.

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Present address: Institut de Génétique et de Biologie Moléculaire et Cellulaire (I.G.B.M.C.), BP 163, 1 rue Fries, 67404 ILLKIRCH Cedex, C.U. de Strasbourg, France.