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Gene Specific Actions of Thyroid Hormone Receptor Subtypes

dc.creatorJaime J. Cantú Pompa
dc.date2013
dc.date.accessioned2018-10-18T21:51:04Z
dc.date.available2018-10-18T21:51:04Z
dc.identifier.issn19326203
dc.identifier.doi10.1371/journal.pone.0052407
dc.identifier.urihttp://hdl.handle.net/11285/630498
dc.descriptionThere 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). © 2013 Lin et al.
dc.languageeng
dc.relationhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-84871867985&doi=10.1371%2fjournal.pone.0052407&partnerID=40&md5=31a7c2bd4b7751fe0e5f6403c14cdca0
dc.relationInvestigadores
dc.relationEstudiantes
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0
dc.sourcePLoS ONE
dc.subjectcycloheximide
dc.subjectliothyronine
dc.subjectthyroid hormone receptor alpha
dc.subjectthyroid hormone receptor beta
dc.subjectarticle
dc.subjectcell strain HepG2
dc.subjectcontrolled study
dc.subjectgene control
dc.subjectgene targeting
dc.subjectgenetic variability
dc.subjectHeLa cell
dc.subjectprotein expression
dc.subjectprotein function
dc.subjectCycloheximide
dc.subjectDNA, Complementary
dc.subjectGene Expression Profiling
dc.subjectGene Expression Regulation
dc.subjectHeLa Cells
dc.subjectHep G2 Cells
dc.subjectHumans
dc.subjectKinetics
dc.subjectModels, Biological
dc.subjectOligonucleotide Array Sequence Analysis
dc.subjectThyroid Hormone Receptors alpha
dc.subjectThyroid Hormone Receptors beta
dc.subjectTriiodothyronine
dc.subject.classification7 INGENIERÍA Y TECNOLOGÍA
dc.titleGene Specific Actions of Thyroid Hormone Receptor Subtypes
dc.typeArtículo
dc.identifier.volume8
dc.identifier.issue1
refterms.dateFOA2018-10-18T21:51:04Z


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