DLX3 interacts with GCM1 and inhibits its transactivation-stimulating activity in a homeodomain-dependent manner in human trophoblast-derived cells

Abstract The placental transcription factors Distal-less 3 (DLX3) and Glial cell missing-1 (GCM1) have been shown to coordinate the specific regulation of PGF in human trophoblast cell lines. While both factors independently have a positive effect on PGF gene expression, when combined, DLX3 acts as...

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Autores principales:	Sha Li, Mark S. Roberson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7177716d0eb14b81a3fc83cdaf09e1fc
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spelling	oai:doaj.org-article:7177716d0eb14b81a3fc83cdaf09e1fc2021-12-02T11:40:14ZDLX3 interacts with GCM1 and inhibits its transactivation-stimulating activity in a homeodomain-dependent manner in human trophoblast-derived cells10.1038/s41598-017-02120-52045-2322https://doaj.org/article/7177716d0eb14b81a3fc83cdaf09e1fc2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02120-5https://doaj.org/toc/2045-2322Abstract The placental transcription factors Distal-less 3 (DLX3) and Glial cell missing-1 (GCM1) have been shown to coordinate the specific regulation of PGF in human trophoblast cell lines. While both factors independently have a positive effect on PGF gene expression, when combined, DLX3 acts as an antagonist to GCM. Despite this understanding, potential mechanisms accounting for this regulatory interaction remain unexplored. We identify physical and functional interactions between specific domains of DLX3 and GCM1 in human trophoblast-derived cells by performing immunoprecipitation and mammalian one hybrid assays. Studies revealed that DLX3 binding reduced the transcriptional activity of GCM1, providing a mechanistic explanation of their functional antagonism in regulating PGF promoter activity. The DLX3 homeodomain (HD) was essential for DLX3-GCM1 interaction, and that the HD together with the DLX3 amino- or carboxyl-terminal domains was required for maximal inhibition of GCM1. Interestingly, a naturally occurring DLX3 mutant that disrupts the carboxyl-terminal domain leading to tricho-dento-osseous syndrome in humans displayed activities indistinguishable from wild type DLX3 in this system. Collectively, our studies demonstrate that DLX3 physically interacts with GCM1 and inhibits its transactivation activity, suggesting that DLX3 and GCM1 may form a complex to functionally regulate placental cell function through modulation of target gene expression.Sha LiMark S. RobersonNature 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 Sha Li Mark S. Roberson DLX3 interacts with GCM1 and inhibits its transactivation-stimulating activity in a homeodomain-dependent manner in human trophoblast-derived cells
description	Abstract The placental transcription factors Distal-less 3 (DLX3) and Glial cell missing-1 (GCM1) have been shown to coordinate the specific regulation of PGF in human trophoblast cell lines. While both factors independently have a positive effect on PGF gene expression, when combined, DLX3 acts as an antagonist to GCM. Despite this understanding, potential mechanisms accounting for this regulatory interaction remain unexplored. We identify physical and functional interactions between specific domains of DLX3 and GCM1 in human trophoblast-derived cells by performing immunoprecipitation and mammalian one hybrid assays. Studies revealed that DLX3 binding reduced the transcriptional activity of GCM1, providing a mechanistic explanation of their functional antagonism in regulating PGF promoter activity. The DLX3 homeodomain (HD) was essential for DLX3-GCM1 interaction, and that the HD together with the DLX3 amino- or carboxyl-terminal domains was required for maximal inhibition of GCM1. Interestingly, a naturally occurring DLX3 mutant that disrupts the carboxyl-terminal domain leading to tricho-dento-osseous syndrome in humans displayed activities indistinguishable from wild type DLX3 in this system. Collectively, our studies demonstrate that DLX3 physically interacts with GCM1 and inhibits its transactivation activity, suggesting that DLX3 and GCM1 may form a complex to functionally regulate placental cell function through modulation of target gene expression.
format	article
author	Sha Li Mark S. Roberson
author_facet	Sha Li Mark S. Roberson
author_sort	Sha Li
title	DLX3 interacts with GCM1 and inhibits its transactivation-stimulating activity in a homeodomain-dependent manner in human trophoblast-derived cells
title_short	DLX3 interacts with GCM1 and inhibits its transactivation-stimulating activity in a homeodomain-dependent manner in human trophoblast-derived cells
title_full	DLX3 interacts with GCM1 and inhibits its transactivation-stimulating activity in a homeodomain-dependent manner in human trophoblast-derived cells
title_fullStr	DLX3 interacts with GCM1 and inhibits its transactivation-stimulating activity in a homeodomain-dependent manner in human trophoblast-derived cells
title_full_unstemmed	DLX3 interacts with GCM1 and inhibits its transactivation-stimulating activity in a homeodomain-dependent manner in human trophoblast-derived cells
title_sort	dlx3 interacts with gcm1 and inhibits its transactivation-stimulating activity in a homeodomain-dependent manner in human trophoblast-derived cells
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/7177716d0eb14b81a3fc83cdaf09e1fc
work_keys_str_mv	AT shali dlx3interactswithgcm1andinhibitsitstransactivationstimulatingactivityinahomeodomaindependentmannerinhumantrophoblastderivedcells AT marksroberson dlx3interactswithgcm1andinhibitsitstransactivationstimulatingactivityinahomeodomaindependentmannerinhumantrophoblastderivedcells
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DLX3 interacts with GCM1 and inhibits its transactivation-stimulating activity in a homeodomain-dependent manner in human trophoblast-derived cells

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