Increased methylation and decreased expression of homeobox genes TLX1, HOXA10 and DLX5 in human placenta are associated with trophoblast differentiation

Abstract Homeobox 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...

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Autores principales:	Boris Novakovic, Thierry Fournier, Lynda K. Harris, Joanna James, Claire T. Roberts, Hannah E. J. Yong, Bill Kalionis, Danièle Evain-Brion, Peter R. Ebeling, Euan M. Wallace, Richard Saffery, Padma Murthi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/514ca3db682d49198513ba5e866960ce
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spelling	oai:doaj.org-article:514ca3db682d49198513ba5e866960ce2021-12-02T15:06:12ZIncreased methylation and decreased expression of homeobox genes TLX1, HOXA10 and DLX5 in human placenta are associated with trophoblast differentiation10.1038/s41598-017-04776-52045-2322https://doaj.org/article/514ca3db682d49198513ba5e866960ce2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04776-5https://doaj.org/toc/2045-2322Abstract Homeobox 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.Boris NovakovicThierry FournierLynda K. HarrisJoanna JamesClaire T. RobertsHannah E. J. YongBill KalionisDanièle Evain-BrionPeter R. EbelingEuan M. WallaceRichard SafferyPadma MurthiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Boris Novakovic Thierry Fournier Lynda K. Harris Joanna James Claire T. Roberts Hannah E. J. Yong Bill Kalionis Danièle Evain-Brion Peter R. Ebeling Euan M. Wallace Richard Saffery Padma Murthi Increased methylation and decreased expression of homeobox genes TLX1, HOXA10 and DLX5 in human placenta are associated with trophoblast differentiation
description	Abstract Homeobox 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.
format	article
author	Boris Novakovic Thierry Fournier Lynda K. Harris Joanna James Claire T. Roberts Hannah E. J. Yong Bill Kalionis Danièle Evain-Brion Peter R. Ebeling Euan M. Wallace Richard Saffery Padma Murthi
author_facet	Boris Novakovic Thierry Fournier Lynda K. Harris Joanna James Claire T. Roberts Hannah E. J. Yong Bill Kalionis Danièle Evain-Brion Peter R. Ebeling Euan M. Wallace Richard Saffery Padma Murthi
author_sort	Boris Novakovic
title	Increased methylation and decreased expression of homeobox genes TLX1, HOXA10 and DLX5 in human placenta are associated with trophoblast differentiation
title_short	Increased methylation and decreased expression of homeobox genes TLX1, HOXA10 and DLX5 in human placenta are associated with trophoblast differentiation
title_full	Increased methylation and decreased expression of homeobox genes TLX1, HOXA10 and DLX5 in human placenta are associated with trophoblast differentiation
title_fullStr	Increased methylation and decreased expression of homeobox genes TLX1, HOXA10 and DLX5 in human placenta are associated with trophoblast differentiation
title_full_unstemmed	Increased methylation and decreased expression of homeobox genes TLX1, HOXA10 and DLX5 in human placenta are associated with trophoblast differentiation
title_sort	increased methylation and decreased expression of homeobox genes tlx1, hoxa10 and dlx5 in human placenta are associated with trophoblast differentiation
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/514ca3db682d49198513ba5e866960ce
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Increased methylation and decreased expression of homeobox genes TLX1, HOXA10 and DLX5 in human placenta are associated with trophoblast differentiation

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