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Transcriptional regulation of human T-box 5 gene (TBX5) by bone- and cardiac-related transcription factors

2021-02Journal article Restricted access
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dc.contributor.authorVarela, Débora
dc.contributor.authorConceição, Natércia
dc.contributor.authorCancela, M. Leonor
dc.date.accessioned2021-09-08T10:58:07Z
dc.date.available2021-09-08T10:58:07Z
dc.date.issued2021-02
dc.description.abstractT-box 5 (TBX5) protein belongs to the T-box family whose members play a crucial role in cell-type specification, morphogenesis and organogenesis. TBX5 is a transcription factor important for cardiac development and upper limbs formation and its haploinsufficiency causes Holt-Oram syndrome (HOS). An increase in TBX5 dosage also leads to HOS, suggesting that TBX5 is a dose-sensitive transcription factor that needs to be tightly regulated but the molecular mechanisms involved remain unclear. In this work we report the cloning and functional analysis of human TBX5 promoter region 1 (upstream of exon 1) and promoter region 2 (upstream of exon 2), that probably regulate the transcription of the different transcript variants. In silico analysis showed several binding sites for cardiac and skeletal related transcription factors (TFs) and their functionality was assessed using promoter-luciferase constructions and TF-expressing vectors. MEF2A (Myocyte enhancer factor 2 A) was shown to positively regulate both TBX5 promoters, while EGR1 (early growth response 1) repressed both promoters. SOX9 (SRY (sex determining region Y)-box 9) repressed only the activity of promoter region 2. Interestingly, YY1 (Yin and yang 1) repressed promoter region 1 (that regulates the expression of variant 1 and 3), but activated promoter region 2 (that regulates the expression of variant 4). In conclusion, this work provides novel insights toward the better understanding of TBX5 transcriptional regulation by cardiac- and skeletal-related TFs.
dc.description.sponsorshipPortuguese Foundation for Science and Technology (FCT)Portuguese Foundation for Science and Technology [UIDB/04326/2020]; FCTPortuguese Foundation for Science and TechnologyEuropean Commission [SFRH/BD/141918/2018]
dc.description.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.1016/j.gene.2020.145322
dc.identifier.issn0378-1119
dc.identifier.urihttp://hdl.handle.net/10400.1/17035
dc.language.isoeng
dc.peerreviewedyes
dc.publisherELSEVIER
dc.relationAlgarve Centre for Marine Sciences
dc.relationEpigenetic regulation of ZNF687 in bone cells: elucidation of its role in the progression of Paget’s disease towards giant cell tumor of bone
dc.subjectTranscription regulation
dc.subjectTBX5
dc.subjectSRY (sex determining region Y)-box 9 (SOX9)
dc.subjectMyocyte enhancer factor 2 A (MEF2A)
dc.subjectEarly growth response 1 (EGR1)
dc.subjectYin and yang 1 (YY1)
dc.subjectHolt-Oram syndrome
dc.subject.otherGenetics & Heredity
dc.titleTranscriptional regulation of human T-box 5 gene (TBX5) by bone- and cardiac-related transcription factors
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleAlgarve Centre for Marine Sciences
oaire.awardTitleEpigenetic regulation of ZNF687 in bone cells: elucidation of its role in the progression of Paget’s disease towards giant cell tumor of bone
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04326%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F141918%2F2018/PT
oaire.citation.startPage145322
oaire.citation.titleGene
oaire.citation.volume768
oaire.fundingStream6817 - DCRRNI ID
person.familyNameDomingos Varela
person.familyNameConceição
person.familyNameCancela
person.givenNameDébora Cristina
person.givenNameNatércia
person.givenNameM. Leonor
person.identifier.ciencia-id9A1C-DFE4-98C9
person.identifier.ciencia-id7C11-760D-F425
person.identifier.orcid0000-0002-5057-0912
person.identifier.orcid0000-0003-3114-6662
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsrestrictedAccess
rcaap.typearticle
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