Amphibian metamorphosis, which is controlled by thyroid hormone (TH), is highly temperature-sensitive. Using real-time PCR, we investigated the gene expression profile in the liver of Rana catesbeiana tadpoles kept at 28 and 4 degrees C and treated with 5 nM 3,3',5-triiodothyronine (T3). Out of the 48 genes tested, 12 were up-regulated at 4 degrees C in T3-treated or untreated tadpoles. These included genes involved in energy metabolism, transcription, and translation. Four TH-response genes, including TH receptor beta (TR beta) gene, showed no response to 13 at 4 degrees C. Deiodinase III was the only gene down-regulated at 4 degrees C. Chromatin immunoprecipitation assays showed that CCAAT/enhancer-binding protein 2 gene activation by cold exposure was associated with an increase in the acetylation of histone H3 at lysine 9, whereas TR beta gene activation by T3 at 28 degrees C was associated with an increase in the methylation of histone H3 at lysine 36 with no T3-dependent changes in methylation states on cold exposure. Our results suggest that the transfer of TH signal to chromatin modifications on a primary early TH response gene was specifically blocked by exposure to cold. (C) 2012 Elsevier Inc. All rights reserved.