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Central role of betaine-homocysteine S-methyltransferase 3 in chondral ossification and evidence for sub-functionalization in neoteleost fish

2016-07Journal article Restricted access
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dc.contributor.authorRosa, Joana
dc.contributor.authorTiago, Daniel
dc.contributor.authorMarques, Cátia L.
dc.contributor.authorVijayakumar, Parameswaran
dc.contributor.authorFonseca, Luís
dc.contributor.authorCancela, Leonor
dc.contributor.authorLaizé, Vincent
dc.date.accessioned2017-04-07T15:56:27Z
dc.date.available2017-04-07T15:56:27Z
dc.date.issued2016-07
dc.description.abstractBackground: To better understand the complex mechanisms of bone formation it is fundamental that genes central to signaling/regulatory pathways and matrix formation are identified. Cell systems were used to analyze genes differentially expressed during extracellular matrix mineralization and bhmt3, coding for a betaine-homocysteine S-methyltransferase, was shown to be down-regulated in mineralizing gilthead seabream cells.Methods: Levels and sites of bhmt3 expression were determined by qPCR and in situ hybridization throughout seabream development and in adult tissues. Transcriptional regulation of bhmt3 was assessed from the activity of promoter constructs controlling luciferase gene expression. Molecular phylogeny of vertebrate BHMT was determined from maximum likelihood analysis of available sequences.Results: bhmt3 transcript is abundant in calcified tissues and localized in cartilaginous structures undergoing endo/perichondral ossification. Promoter activity is regulated by transcription factors involved in bone and cartilage development, further demonstrating the central role of Bhmt3 in chondrogenesis and/or osteogenesis. Molecular phylogeny revealed the explosive diversity of bhmt genes in neoteleost fish, while tissue distribution of bhmt genes in seabream suggested that neoteleostean Bhmt may have undergone several steps of sub-functionalization.Conclusions: Data on bhmt3 gene expression and promoter activity evidences a novel function for betaine-homocysteine S-methyltransferase in bone and cartilage development, while phylogenetic analysis provides new insights into the evolution of vertebrate BHMTs and suggests that multiple gene duplication events occurred in neoteleost fish lineage.General significance: High and specific expression of Bhmt3 in gilthead seabream calcified tissues suggests that bone-specific betaine-homocysteine S-methyltransferases could represent a suitable marker of chondral ossification.
dc.identifier.doihttps://doi.org/10.1016/j.bbagen.2016.03.034
dc.identifier.issn0304-4165
dc.identifier.otherAUT: LCA007;
dc.identifier.urihttp://hdl.handle.net/10400.1/9419
dc.language.isoeng
dc.peerreviewedyes
dc.publisherElsevier
dc.relationROLE OF A SHORT CHAIN DEHYDROGENASE/REDUCTASE IN TISSUE MINERALIZATION
dc.relationImpact of microRNAs in skeleton formation and regeneration
dc.relationStrategic Project - LA 15 - 2011-2012
dc.relation.isbasedonWOS:000376829300001
dc.subjectGilthead seabream Sparus aurata
dc.subjectBetaine–homocysteine S-methyltransferase
dc.subjectBone formation
dc.subjectIn vitro mineralization
dc.subjectMolecular evolution
dc.subjectGene expression
dc.subjectTranscriptional regulation
dc.subjectTaxonomic distribution
dc.titleCentral role of betaine-homocysteine S-methyltransferase 3 in chondral ossification and evidence for sub-functionalization in neoteleost fish
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleROLE OF A SHORT CHAIN DEHYDROGENASE/REDUCTASE IN TISSUE MINERALIZATION
oaire.awardTitleImpact of microRNAs in skeleton formation and regeneration
oaire.awardTitleStrategic Project - LA 15 - 2011-2012
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F47433%2F2008/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBPD%2F111289%2F2015/PT
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oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6820 - DCRRNI ID/PEst-C%2FMAR%2FLA0015%2F2011/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FMulti%2F04326%2F2013/PT
oaire.citation.endPage1387
oaire.citation.issue7
oaire.citation.startPage1373
oaire.citation.titleBiochimica et Biophysica Acta - General Subjects
oaire.citation.volume1860
oaire.fundingStreamSFRH
oaire.fundingStream6820 - DCRRNI ID
oaire.fundingStream5876
person.familyNameRosa
person.familyNameTiago
person.familyNameVijayakumar
person.familyNameCancela
person.familyNameLaizé
person.givenNameJoana
person.givenNameDaniel
person.givenNameParameswaran
person.givenNameM. Leonor
person.givenNameVincent
person.identifier.ciencia-id0B18-8AEC-875C
person.identifier.orcid0000-0001-7947-2681
person.identifier.orcid0000-0001-8418-6292
person.identifier.orcid0000-0002-1345-586X
person.identifier.orcid0000-0003-3114-6662
person.identifier.orcid0000-0001-9565-9198
person.identifier.ridE-5298-2017
person.identifier.ridB-4463-2008
person.identifier.scopus-author-id36505067900
person.identifier.scopus-author-id14422711000
person.identifier.scopus-author-id8973850300
person.identifier.scopus-author-id6602982778
project.funder.identifierhttp://doi.org/10.13039/501100001871
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project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
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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