Thyroid hormone receptors (THRs/TRs) belong to the superfamily of ligand-dependent transcription factors. TRs are encoded by the THRA and THRB genes located on chromosomes 3 and 17, respectively. There are two major THR genes, THRA and THRB, that are expressed in a tissuespecific manner. There are two major THRA receptor splice variants (THRA1/TRα1 and THRA2/TRα2) encoded by the THRA gene and two THRB isoforms (THRB1/TRβ1 and THRB2/TRβ2) generated by alternate promoter choice by the THRB gene. THRA1 is highly expressed in the heart, bone, and skeletal muscle whereas THRA2 is widely expressed. The transcriptional activity of the TRs is regulated at multiple levels. 
THRs form heterodimers with retinoid X receptors (RXR), that enable THRs to bind more stably to a wider repertoire of nucleotide sequences. Steroid receptor coactivator (SRC)/NCoA, binds directly to liganded TRs and recruits p300/CBP and p300/CBPassociated factor (p/CAF) which have HAT activity.  THRs also can decrease the expression of negatively-regulated target genes. The transcriptional activity of these genes is increased in the absence of TH and decreased in the presence of TH. THRs also have been shown to interact with several other classes of transcription factor, including NF-1, Oct-1, Sp-1, p53, Pit-1, and CTCF to negatively regulate gene expression, but the mechanism(s) is still largely unknown.