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

Robyn Jimenez, Martin L. Privalsky

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)87-97
Number of pages11
JournalMolecular and Cellular Endocrinology
Volume447
DOIs
StatePublished - May 15 2017

Fingerprint

Thyroid Hormone Resistance Syndrome
Thyroid Hormone Receptors
Thyroid Hormones
Genes
Hormones
Endocrine System Diseases
Disease Resistance
Gene Expression Regulation
Impact resistance
Vertebrates
Gene expression
Transcription Factors
Phenotype

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Cite this

A resistance to thyroid hormone syndrome mutant operates through the target gene repertoire of the wild-type thyroid hormone receptor. / Jimenez, Robyn; Privalsky, Martin L.

In: Molecular and Cellular Endocrinology, Vol. 447, 15.05.2017, p. 87-97.

Research output: Contribution to journalArticle

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