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Genome-wide binding patterns of thyroid hormone receptor beta

dc.creatorJan Antonio Lammel Lindemann
dc.date2014
dc.date.accessioned2018-10-18T20:12:48Z
dc.date.available2018-10-18T20:12:48Z
dc.identifier.issn19326203
dc.identifier.doi10.1371/journal.pone.0081186
dc.identifier.urihttp://hdl.handle.net/11285/630296
dc.descriptionThyroid hormone (TH) receptors (TRs) play central roles in metabolism and are major targets for pharmaceutical intervention. Presently, however, there is limited information about genome wide localizations of TR binding sites. Thus, complexities of TR genomic distribution and links between TRβ binding events and gene regulation are not fully appreciated. Here, we employ a BioChIP approach to capture TR genome-wide binding events in a liver cell line (HepG2). Like other NRs, TRβ appears widely distributed throughout the genome. Nevertheless, there is striking enrichment of TRβ binding sites immediately 5′ and 3′ of transcribed genes and TRβ can be detected near 50% of T3 induced genes. In contrast, no significant enrichment of TRβ is seen at negatively regulated genes or genes that respond to unliganded TRs in this system. Canonical TRE half-sites are present in more than 90% of TRβ peaks and classical TREs are also greatly enriched, but individual TRE organization appears highly variable with diverse half-site orientation and spacing. There is also significant enrichment of binding sites for TR associated transcription factors, including AP-1 and CTCF, near TR peaks. We conclude that T3-dependent gene induction commonly involves proximal TRβ binding events but that far-distant binding events are needed for T3 induction of some genes and that distinct, indirect, mechanisms are often at play in negative regulation and unliganded TR actions. Better understanding of genomic context of TR binding sites will help us determine why TR regulates genes in different ways and determine possibilities for selective modulation of TR action. © 2014 Ayers et al.
dc.languageeng
dc.relationhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-84897585437&doi=10.1371%2fjournal.pone.0081186&partnerID=40&md5=87a4c921150be424d4e02990e2fc0580
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.subjectthyroid hormone receptor beta
dc.subjecttranscription factor AP 1
dc.subjecttranscription factor CTCF
dc.subjectligand
dc.subjectprotein binding
dc.subjectRNA
dc.subjectthyroid hormone receptor beta
dc.subject3' untranslated region
dc.subject5' untranslated region
dc.subjectanimal experiment
dc.subjectanimal tissue
dc.subjectarticle
dc.subjectbinding kinetics
dc.subjectbinding site
dc.subjectcontrolled study
dc.subjectgene cluster
dc.subjectgene control
dc.subjectgene expression
dc.subjectgene repression
dc.subjectgene sequence
dc.subjectgene targeting
dc.subjectgenetic association
dc.subjectgenetic transcription
dc.subjectgenetic transfection
dc.subjecthuman
dc.subjecthuman cell
dc.subjectliver cell
dc.subjectmouse
dc.subjectnonhuman
dc.subjectnucleotide sequence
dc.subjectprotein analysis
dc.subjectprotein function
dc.subjectprotein localization
dc.subjectsequence analysis
dc.subjectanimal
dc.subjectbinding site
dc.subjectC57BL mouse
dc.subjectcell line
dc.subjectchemistry
dc.subjectDNA microarray
dc.subjectDNA responsive element
dc.subjectDNA sequence
dc.subjectgene expression regulation
dc.subjectgenome
dc.subjectHepG2 cell line
dc.subjectliver
dc.subjectmetabolism
dc.subjectmultigene family
dc.subjectplasmid
dc.subjectAnimals
dc.subjectBinding Sites
dc.subjectCell Line
dc.subjectGene Expression Regulation
dc.subjectGenome
dc.subjectHep G2 Cells
dc.subjectHumans
dc.subjectLigands
dc.subjectLiver
dc.subjectMice
dc.subjectMice, Inbred C57BL
dc.subjectMultigene Family
dc.subjectOligonucleotide Array Sequence Analysis
dc.subjectPlasmids
dc.subjectProtein Binding
dc.subjectResponse Elements
dc.subjectRNA
dc.subjectSequence Analysis, DNA
dc.subjectThyroid Hormone Receptors beta
dc.subject.classification7 INGENIERÍA Y TECNOLOGÍA
dc.titleGenome-wide binding patterns of thyroid hormone receptor beta
dc.typeArtículo
dc.identifier.volume9
dc.identifier.issue2
refterms.dateFOA2018-10-18T20:12:48Z


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