A resistance to thyroid hormone syndrome mutant operates through the target gene repertoire of the wild-type thyroid hormone receptor

作者：Jimenez Robyn; Privalsky Martin L^*

来源：Molecular and Cellular Endocrinology, 2017, 447(C): 87-97.

DOI：10.1016/j.mce.2017.02.044

• Thyroid hormone receptor
• Target genes
• RTH
• RNA-seq
• Endocrine disease

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-TR beta 1 mutant (R429Q) to those regulated by WT-TR beta 1. With only a few potential exceptions, the vast majority of genes we were able to identify as regulated by the WT-TR beta 1, positively or negatively, were also regulated by the RTH-TR beta 1 mutant. We conclude that the actions of R429Q-TR beta 1 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.

• 出版日期2017-5-15