A resistance to thyroid hormone syndrome mutant operates through the target gene repertoire of the wild-type thyroid hormone receptor.
Thyroid hormone receptors (TRs) play crucial roles in vertebrates. Wild-type (WT) TRs function primarily as hormone-regulated transcription factors. A human endocrine disease, Resistance to Thyroid Hormone (RTH)-Syndrome, is caused by inheritance of mutant TRs impaired in the proper regulation of target gene expression. To better understand the molecular basis of RTH we compared the target genes regulated by an RTH-TRβ1 mutant (R429Q) to those regulated by WT-TRβ1. With only a few potential exceptions, the vast majority of genes we were able to identify as regulated by the WT-TRβ1, positively or negatively, were also regulated by the RTH-TRβ1 mutant. We conclude that the actions of R429Q-TRβ1 in RTH-Syndrome most likely reflect the reduced hormone affinity observed for this mutant rather than an alteration in target gene repertoire. Our results highlight the importance of target gene specificity in defining the disease phenotype and improve our understanding of how clinical treatments impact RTH-Syndrome.
['Jimenez|Robyn|R|', 'Privalsky|Martin L|ML|']
D000256:Adenoviridae D005786:Gene Expression Regulation D063990:Gene Ontology D005822:Genetic Vectors D057809:HEK293 Cells D056945:Hep G2 Cells D006801:Humans D050505:Mutant Proteins D009154:Mutation D011988:Receptors, Thyroid Hormone D015398:Signal Transduction D018382:Thyroid Hormone Resistance Syndrome D014284:Triiodothyronine
Target genes Thyroid hormone receptor Endocrine disease RTH RNA-seq