DNA methylation of specific CpG sites in the promoter region regulates the transcription of the mouse oxytocin receptor.

Oxytocin is a peptide hormone, well known for its role in labor and suckling, and most recently for its involvement in mammalian social behavior. All central and peripheral actions of oxytocin are mediated through the oxytocin receptor, which is the product of a single gene. Transcription of the oxy...

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Main Authors: Shimrat Mamrut, Hala Harony, Rapita Sood, Hadar Shahar-Gold, Harold Gainer, Yi-Jun Shi, Liza Barki-Harrington, Shlomo Wagner
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3575498?pdf=render
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spelling doaj-007594b7faf542148b50030491127c4f2020-11-25T01:15:44ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0182e5686910.1371/journal.pone.0056869DNA methylation of specific CpG sites in the promoter region regulates the transcription of the mouse oxytocin receptor.Shimrat MamrutHala HaronyRapita SoodHadar Shahar-GoldHarold GainerYi-Jun ShiLiza Barki-HarringtonShlomo WagnerOxytocin is a peptide hormone, well known for its role in labor and suckling, and most recently for its involvement in mammalian social behavior. All central and peripheral actions of oxytocin are mediated through the oxytocin receptor, which is the product of a single gene. Transcription of the oxytocin receptor is subject to regulation by gonadal steroid hormones, and is profoundly elevated in the uterus and mammary glands during parturition. DNA methylation is a major epigenetic mechanism that regulates gene transcription, and has been linked to reduced expression of the oxytocin receptor in individuals with autism. Here, we hypothesized that transcription of the mouse oxytocin receptor is regulated by DNA methylation of specific sites in its promoter, in a tissue-specific manner. Hypothalamus-derived GT1-7, and mammary-derived 4T1 murine cell lines displayed negative correlations between oxytocin receptor transcription and methylation of the gene promoter, and demethylation caused a significant enhancement of oxytocin receptor transcription in 4T1 cells. Using a reporter gene assay, we showed that methylation of specific sites in the gene promoter, including an estrogen response element, significantly inhibits transcription. Furthermore, methylation of the oxytocin receptor promoter was found to be differentially correlated with oxytocin receptor expression in mammary glands and the uterus of virgin and post-partum mice, suggesting that it plays a distinct role in oxytocin receptor transcription among tissues and under different physiological conditions. Together, these results support the hypothesis that the expression of the mouse oxytocin receptor gene is epigenetically regulated by DNA methylation of its promoter.http://europepmc.org/articles/PMC3575498?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Shimrat Mamrut
Hala Harony
Rapita Sood
Hadar Shahar-Gold
Harold Gainer
Yi-Jun Shi
Liza Barki-Harrington
Shlomo Wagner
spellingShingle Shimrat Mamrut
Hala Harony
Rapita Sood
Hadar Shahar-Gold
Harold Gainer
Yi-Jun Shi
Liza Barki-Harrington
Shlomo Wagner
DNA methylation of specific CpG sites in the promoter region regulates the transcription of the mouse oxytocin receptor.
PLoS ONE
author_facet Shimrat Mamrut
Hala Harony
Rapita Sood
Hadar Shahar-Gold
Harold Gainer
Yi-Jun Shi
Liza Barki-Harrington
Shlomo Wagner
author_sort Shimrat Mamrut
title DNA methylation of specific CpG sites in the promoter region regulates the transcription of the mouse oxytocin receptor.
title_short DNA methylation of specific CpG sites in the promoter region regulates the transcription of the mouse oxytocin receptor.
title_full DNA methylation of specific CpG sites in the promoter region regulates the transcription of the mouse oxytocin receptor.
title_fullStr DNA methylation of specific CpG sites in the promoter region regulates the transcription of the mouse oxytocin receptor.
title_full_unstemmed DNA methylation of specific CpG sites in the promoter region regulates the transcription of the mouse oxytocin receptor.
title_sort dna methylation of specific cpg sites in the promoter region regulates the transcription of the mouse oxytocin receptor.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2013-01-01
description Oxytocin is a peptide hormone, well known for its role in labor and suckling, and most recently for its involvement in mammalian social behavior. All central and peripheral actions of oxytocin are mediated through the oxytocin receptor, which is the product of a single gene. Transcription of the oxytocin receptor is subject to regulation by gonadal steroid hormones, and is profoundly elevated in the uterus and mammary glands during parturition. DNA methylation is a major epigenetic mechanism that regulates gene transcription, and has been linked to reduced expression of the oxytocin receptor in individuals with autism. Here, we hypothesized that transcription of the mouse oxytocin receptor is regulated by DNA methylation of specific sites in its promoter, in a tissue-specific manner. Hypothalamus-derived GT1-7, and mammary-derived 4T1 murine cell lines displayed negative correlations between oxytocin receptor transcription and methylation of the gene promoter, and demethylation caused a significant enhancement of oxytocin receptor transcription in 4T1 cells. Using a reporter gene assay, we showed that methylation of specific sites in the gene promoter, including an estrogen response element, significantly inhibits transcription. Furthermore, methylation of the oxytocin receptor promoter was found to be differentially correlated with oxytocin receptor expression in mammary glands and the uterus of virgin and post-partum mice, suggesting that it plays a distinct role in oxytocin receptor transcription among tissues and under different physiological conditions. Together, these results support the hypothesis that the expression of the mouse oxytocin receptor gene is epigenetically regulated by DNA methylation of its promoter.
url http://europepmc.org/articles/PMC3575498?pdf=render
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