Please use this identifier to cite or link to this item: https://biore.bio.bg.ac.rs/handle/123456789/6432
Title: Gene specific actions of thyroid hormone receptor subtypes
Authors: Lin, Jean Z.
Sieglaff, Douglas H.
Yuan, Chaoshen
Su, Jing
Arumanayagam, AnithaChristy S.
Firouzbakht, Sharareh
Cantu Pompa, Jaime J.
Denoto Reynolds, Frances
Zhou, Xiabo
Čvoro, Aleksandra 
Webb, Paul
Issue Date: 2013
Rank: M21
Journal: PLoS One
Volume: 8
Issue: 1
Start page: e52407
Abstract: 
There are two homologous thyroid hormone (TH) receptors (TRs α and β), which are members of the nuclear hormone receptor (NR) family. While TRs regulate different processes in vivo and other highly related NRs regulate distinct gene sets, initial studies of TR action revealed near complete overlaps in their actions at the level of individual genes. Here, we assessed the extent that TRα and TRβ differ in target gene regulation by comparing effects of equal levels of stably expressed exogenous TRs +/− T3 in two cell backgrounds (HepG2 and HeLa). We find that hundreds of genes respond to T3 or to unliganded TRs in both cell types, but were not able to detect verifiable examples of completely TR subtype-specific gene regulation. TR actions are, however, far from identical and we detect TR subtype-specific effects on global T3 response kinetics in HepG2 cells and many examples of TR subtype specificity at the level of individual genes, including effects on magnitude of response to TR +/− T3, TR regulation patterns and T3 dose response. Cycloheximide (CHX) treatment confirms that at least some differential effects involve verifiable direct TR target genes. TR subtype/gene-specific effects emerge in the context of widespread variation in target gene response and we suggest that gene-selective effects on mechanism of TR action highlight differences in TR subtype function that emerge in the environment of specific genes. We propose that differential TR actions could influence physiologic and pharmacologic responses to THs and selective TR modulators (STRMs).
URI: https://biore.bio.bg.ac.rs/handle/123456789/6432
DOI: 10.1371/journal.pone.0052407
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