Effects of ligand and thyroid hormone receptor isoforms on hepatic gene expression profiles of thyroid hormone receptor knockout mice

We used cDNA microarrays to study hepatic gene profiles in hypothyroid and hyperthyroid mice, and we identified more than 50 target genes, which are involved in a range of cellular pathways

Paul M Yen; Xu Feng; Frederic Flamant; Yidong Chen; Robert L Walker; Roy E Weiss; Olivier Chassande; Jacques Samarut; Samuel Refetoff; Paul S Meltzer


Scholarcy highlights

  • 3,3’,5-Triiodothyronine, the active thyroid hormone metabolite of thyroxine, affects differentiation, growth and cellular metabolism. It binds to two Th receptor isoforms, Tr-α and Tr-β, which are encoded by separate genes and mediate Th-regulated gene expression by binding to Th response elements in the promoter regions of target genes
  • In the absence of Th, Trs recruit co-repressor complexes and silencing mediator of Tr and retinoic acid receptor) that lead to the histone deacetylation of local chromatin in the promoter region, and decrease the basal transcription of positively regulated target genes
  • Hepatic RNA from mice treated with propythiouracil and T3, or treated with T3 alone, was compared to hepatic RNA from euthyroid wild-type mice
  • 64 probes that corresponded to 57 genes increased by greater than 1.5-fold, and 34 probes corresponding to 30 genes decreased by at least 60% when compared to wild-type euthyroid mRNA expression
  • We previously showed that there is a high level of correlation between cDNA microarrays and northern blot analyses in determining the expression of several target genes
  • Studies with the Thra/ Thrb double-knockout mice showed that absence of Th receptor had a different effect on the pattern of gene expression than did the absence of ligand

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