%0 Journal Article
%T Identification of thyroid hormone response elements in vivo using mice expressing a tagged thyroid hormone receptor ¦Á1
%A Susi Dudazy£¿Gralla
%A Kristina Nordstr£¿m
%A Peter£¿Josef Hofmann
%A Dina£¿Abdul Meseh
%J Bioscience Reports
%D 2013
%I Portland Press, Biochemical Society
%R 10.1042/bsr20120124
%X TR¦Á1 (thyroid hormone receptor ¦Á1) 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¦Á1 for ChIP (chromatin immunoprecipitation), only a few direct TR¦Á1 target genes have been identified in the brain. Here we demonstrate that mice expressing a TR¦Á1¨CGFP (green fluorescent protein) fusion protein from the endogenous TR¦Á locus provide a valuable animal model to identify TR¦Á1 target genes. To this end, we analysed DNA¨CTR¦Á1 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 TR¦Á1 target genes in brain and heart. Moreover, our model system enabled the identification of novel TR¦Á1 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¨CDNA interactions in vivo, circumventing the need for specific antibodies. Models like the TR¦Á1¨CGFP 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.
%K brain
%K hyperthyroidism
%K hypothyroidism
%K thyroid hormone receptor
%K thyroid hormone response element
%U http://www.bioscirep.org/bsr/033/e027/bsr033e027.htm