Distinct ligand-dependent and independent modes of thyroid hormone receptor (TR)/PGC-1α interaction

Chaoshen Yuan, Phuong Nguyen, John D. Baxter, Paul Webb

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Thyroid hormone receptor (TR)/peroxisome proliferator activated receptor coactivator (PGC-1α) interactions are required for T3-dependent transcriptional responses involved in adaptive thermogenesis and liver. Thus, it is important to define TR/PGC-1α contact modes and to understand their significance in gene expression. Previous studies have shown that TRβ1 recruits PGC-1α to target promoters via contacts between the hormone-dependent TRβ1 activation function 2 (AF-2) in the C-terminal ligand binding domain (LBD) and a major PGC-1α nuclear receptor (NR) interaction box (consensus LxxLL) at amino acids 142-146. While our studies verify the existence and importance of this interaction, we present evidence that TRβ1 also binds PGC-1α in a second ligand and LxxLL motif independent mode and show that this interaction requires the TRβ1 N-terminal domain (NTD) and the PGC-1α N-terminal activation domain (AD) at amino acids 1-130. Transfection assays suggest that optimal PGC-1α coactivation requires the TRβ1 NTD and that these contacts are needed for utilization of the PGC-1α C-terminal AD, which does not bind TR and is implicated in basal transcription machinery contacts. We propose that TR AF-1/PGC-1α contacts are needed for transition between activities of PGC-1α N-and C-terminal ADs in gene expression. Our findings provide insights into possible roles for TR and NR AF-1 in gene expression.

Original languageEnglish (US)
Pages (from-to)58-65
Number of pages8
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume133
Issue number1
DOIs
StatePublished - Jan 2013

Keywords

  • Activation function
  • Coactivator
  • Gene expression
  • Peroxisome proliferator activated receptor coactivators
  • Thyroid hormone
  • Thyroid hormone receptors

ASJC Scopus subject areas

  • Molecular Medicine
  • Endocrinology, Diabetes and Metabolism
  • Molecular Biology
  • Cell Biology
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry

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