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dc.contributor.authorNovakovic, B
dc.contributor.authorFournier, T
dc.contributor.authorHarris, LK
dc.contributor.authorJames, J
dc.contributor.authorRoberts, CT
dc.contributor.authorYong, HEJ
dc.contributor.authorKalionis, B
dc.contributor.authorEvain-Brion, D
dc.contributor.authorEbeling, PR
dc.contributor.authorWallace, EM
dc.contributor.authorSaffery, R
dc.contributor.authorMurthi, P
dc.date.accessioned2021-02-04T02:12:46Z
dc.date.available2021-02-04T02:12:46Z
dc.date.issued2017-07-03
dc.identifierpii: 10.1038/s41598-017-04776-5
dc.identifier.citationNovakovic, B., Fournier, T., Harris, L. K., James, J., Roberts, C. T., Yong, H. E. J., Kalionis, B., Evain-Brion, D., Ebeling, P. R., Wallace, E. M., Saffery, R. & Murthi, P. (2017). Increased methylation and decreased expression of homeobox genes TLX1, HOXA10 and DLX5 in human placenta are associated with trophoblast differentiation. SCIENTIFIC REPORTS, 7 (1), https://doi.org/10.1038/s41598-017-04776-5.
dc.identifier.issn2045-2322
dc.identifier.urihttp://hdl.handle.net/11343/259610
dc.description.abstractHomeobox genes regulate embryonic and placental development, and are widely expressed in the human placenta, but their regulatory control by DNA methylation is unclear. DNA methylation analysis was performed on human placentae from first, second and third trimesters to determine methylation patterns of homeobox gene promoters across gestation. Most homeobox genes were hypo-methylated throughout gestation, suggesting that DNA methylation is not the primary mechanism involved in regulating HOX genes expression in the placenta. Nevertheless, several genes showed variable methylation patterns across gestation, with a general trend towards an increase in methylation over gestation. Three genes (TLX1, HOXA10 and DLX5) showed inverse gains of methylation with decreasing mRNA expression throughout pregnancy, supporting a role for DNA methylation in their regulation. Proteins encoded by these genes were primarily localised to the syncytiotrophoblast layer, and showed decreased expression later in gestation. siRNA mediated downregulation of DLX5, TLX1 and HOXA10 in primary term villous cytotrophoblast resulted in decreased proliferation and increased expression of differentiation markers, including ERVW-1. Our data suggest that loss of DLX5, TLX1 and HOXA10 expression in late gestation is required for proper placental differentiation and function.
dc.languageEnglish
dc.publisherNATURE PUBLISHING GROUP
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleIncreased methylation and decreased expression of homeobox genes TLX1, HOXA10 and DLX5 in human placenta are associated with trophoblast differentiation
dc.typeJournal Article
dc.identifier.doi10.1038/s41598-017-04776-5
melbourne.affiliation.departmentObstetrics and Gynaecology
melbourne.affiliation.departmentPaediatrics (RCH)
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titleScientific Reports
melbourne.source.volume7
melbourne.source.issue1
melbourne.identifier.nhmrc509140
dc.rights.licenseCC BY
melbourne.elementsid1220114
melbourne.contributor.authorKalionis, Bill
melbourne.contributor.authorMurthi, Padma
melbourne.contributor.authorSaffery, Richard
melbourne.contributor.authorYong, Ee
dc.identifier.eissn2045-2322
melbourne.identifier.fundernameidNHMRC, 509140
melbourne.accessrightsOpen Access


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