title: Identification of thyroid hormone response elements in vivo using mice expressing a tagged thyroid hormone receptor α1.
abstract: TRα1 (thyroid hormone receptor α1) 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 TRα1 for ChIP (chromatin immunoprecipitation), only a few direct TRα1 target genes have been identified in the brain. Here we demonstrate that mice expressing a TRα1-GFP (green fluorescent protein) fusion protein from the endogenous TRα locus provide a valuable animal model to identify TRα1 target genes. To this end, we analysed DNA-TRα1 interactions in 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 TRα1 target genes in brain and heart. Moreover, our model system enabled the identification of novel TRα1 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-DNA interactions in vivo, circumventing the need for specific antibodies. Models like the TRα1-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 vivo.
authors: *Department of Cell and Molecular Biology, Karolinska Institute, von Eulers väg 3, 17177 Stockholm, Sweden.
authors: Susi
authors: S
authors: Dudazy-Gralla
authors: *Department of Cell and Molecular Biology, Karolinska Institute, von Eulers väg 3, 17177 Stockholm, Sweden.
authors: Kristina
authors: K
authors: Nordström
authors: †Institut fuer Experimentelle Endokrinologie, Charité Universitätsmedizin, Augustenburger Platz 1, 13353 Berlin, Germany.
authors: Peter Josef
authors: PJ
authors: Hofmann
authors: *Department of Cell and Molecular Biology, Karolinska Institute, von Eulers väg 3, 17177 Stockholm, Sweden.
authors: Dina Abdul
authors: DA
authors: Meseh
authors: †Institut fuer Experimentelle Endokrinologie, Charité Universitätsmedizin, Augustenburger Platz 1, 13353 Berlin, Germany.
authors: Lutz
authors: L
authors: Schomburg
authors: *Department of Cell and Molecular Biology, Karolinska Institute, von Eulers väg 3, 17177 Stockholm, Sweden.
authors: Björn
authors: B
authors: Vennström
authors: *Department of Cell and Molecular Biology, Karolinska Institute, von Eulers väg 3, 17177 Stockholm, Sweden.
authors: Jens
authors: J
authors: Mittag
mesh_terms: D000818:Animals; D047369:Chromatin Immunoprecipitation; D004247:DNA / Q000235:genetics / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000737:chemistry; D051379:Mice; D008822:Mice, Transgenic; D020218:Response Elements / Q000235:genetics*; D037021:Thyroid Hormone Receptors alpha / Q000737:chemistry / Q000235:genetics*; D013963:Thyroid Hormones / Q000235:genetics* / Q000302:isolation & purification; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: D037021:Thyroid Hormone Receptors alpha; D013963:Thyroid Hormones; D049452:Green Fluorescent Proteins; D004247:DNA
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