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TR&#x03B1;1 (thyroid hormone receptor &#x03B1;1) is well recognized for its importance in brain development. However, due to the difficulties in predicting TREs (thyroid hormone response elements) in silico and the lack of suitable antibodies against TR&#x03B1;1 for ChIP (chromatin immunoprecipitation), only a few direct TR&#x03B1;1 target genes have been identified in the brain. Here we demonstrate that mice expressing a TR&#x03B1;1&#x2013;GFP (green fluorescent protein) fusion protein from the endogenous TR&#x03B1; locus provide a valuable animal model to identify TR&#x03B1;1 target genes. To this end, we analysed DNA&#x2013;TR&#x03B1;1 interactions in&#x00A0;vivo using ChIP with an anti-GFP antibody. We validated our system using established TREs from neurogranin and hairless, and by verifying additional TREs from known TR&#x03B1;1 target genes in brain and heart. Moreover, our model system enabled the identification of novel TR&#x03B1;1 target genes such as RNF166 (ring finger protein 166). Our results demonstrate that transgenic mice expressing a tagged nuclear receptor constitute a feasible approach to study receptor&#x2013;DNA interactions in&#x00A0;vivo, circumventing the need for specific antibodies. Models like the TR&#x03B1;1&#x2013;GFP mice may thus pave the way for genome-wide mapping of nuclear receptor-binding sites, and advance the identification of novel target genes in&#x00A0;vivo

Identification of thyroid hormone response elements in vivo using mice expressing a tagged thyroid hormone receptor α1