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Genetic-epigenetic dysregulation of thymic TSH receptor gene expression triggers thyroid autoimmunity

Graves disease (GD) is an autoimmune condition caused by interacting genetic and environmental factors. Genetic studies have mapped several single-nucleotide polymorphisms (SNPs) that are strongly associated with GD, but the mechanisms by which they trigger disease are unknown. We hypothesized that... Full description

Journal Title: Proceedings of the National Academy of Sciences of the United States of America 26 August 2014, Vol.111(34), pp.12562-7
Main Author: Stefan, Mihaela
Other Authors: Wei, Chengguo , Lombardi, Angela , Li, Cheuk Wun , Concepcion, Erlinda S , Inabnet, William B , Owen, Randall , Zhang, Weijia , Tomer, Yaron
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1091-6490 ; PMID: 25122677 Version:1 ; DOI: 10.1073/pnas.1408821111
Link: http://pubmed.gov/25122677
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recordid: medline25122677
title: Genetic-epigenetic dysregulation of thymic TSH receptor gene expression triggers thyroid autoimmunity
format: Article
creator:
  • Stefan, Mihaela
  • Wei, Chengguo
  • Lombardi, Angela
  • Li, Cheuk Wun
  • Concepcion, Erlinda S
  • Inabnet, William B
  • Owen, Randall
  • Zhang, Weijia
  • Tomer, Yaron
subjects:
  • Histone Modifications
  • Interferon
  • Thyroiditis
  • Autoimmunity -- Genetics
  • Graves Disease -- Genetics
  • Receptors, Thyrotropin -- Genetics
ispartof: Proceedings of the National Academy of Sciences of the United States of America, 26 August 2014, Vol.111(34), pp.12562-7
description: Graves disease (GD) is an autoimmune condition caused by interacting genetic and environmental factors. Genetic studies have mapped several single-nucleotide polymorphisms (SNPs) that are strongly associated with GD, but the mechanisms by which they trigger disease are unknown. We hypothesized that epigenetic modifications induced by microenvironmental influences of cytokines can reveal the functionality of GD-associated SNPs. We analyzed genome-wide histone H3 lysine 4 methylation and gene expression in thyroid cells induced by IFNα, a key cytokine secreted during viral infections, and overlapped them with known GD-associated SNPs. We mapped an open chromatin region overlapping two adjacent GD-associated SNPs (rs12101255 and rs12101261) in intron 1 of the thyroid stimulating hormone receptor (TSHR) gene. We then demonstrated that this region functions as a regulatory element through binding of the transcriptional repressor promyelocytic leukemia zinc finger protein (PLZF) at the rs12101261...
language: eng
source:
identifier: E-ISSN: 1091-6490 ; PMID: 25122677 Version:1 ; DOI: 10.1073/pnas.1408821111
fulltext: fulltext
issn:
  • 10916490
  • 1091-6490
url: Link


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titleGenetic-epigenetic dysregulation of thymic TSH receptor gene expression triggers thyroid autoimmunity
creatorStefan, Mihaela ; Wei, Chengguo ; Lombardi, Angela ; Li, Cheuk Wun ; Concepcion, Erlinda S ; Inabnet, William B ; Owen, Randall ; Zhang, Weijia ; Tomer, Yaron
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subjectHistone Modifications ; Interferon ; Thyroiditis ; Autoimmunity -- Genetics ; Graves Disease -- Genetics ; Receptors, Thyrotropin -- Genetics
descriptionGraves disease (GD) is an autoimmune condition caused by interacting genetic and environmental factors. Genetic studies have mapped several single-nucleotide polymorphisms (SNPs) that are strongly associated with GD, but the mechanisms by which they trigger disease are unknown. We hypothesized that epigenetic modifications induced by microenvironmental influences of cytokines can reveal the functionality of GD-associated SNPs. We analyzed genome-wide histone H3 lysine 4 methylation and gene expression in thyroid cells induced by IFNα, a key cytokine secreted during viral infections, and overlapped them with known GD-associated SNPs. We mapped an open chromatin region overlapping two adjacent GD-associated SNPs (rs12101255 and rs12101261) in intron 1 of the thyroid stimulating hormone receptor (TSHR) gene. We then demonstrated that this region functions as a regulatory element through binding of the transcriptional repressor promyelocytic leukemia zinc finger protein (PLZF) at the rs12101261...
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titleGenetic-epigenetic dysregulation of thymic TSH receptor gene expression triggers thyroid autoimmunity
descriptionGraves disease (GD) is an autoimmune condition caused by interacting genetic and environmental factors. Genetic studies have mapped several single-nucleotide polymorphisms (SNPs) that are strongly associated with GD, but the mechanisms by which they trigger disease are unknown. We hypothesized that epigenetic modifications induced by microenvironmental influences of cytokines can reveal the functionality of GD-associated SNPs. We analyzed genome-wide histone H3 lysine 4 methylation and gene expression in thyroid cells induced by IFNα, a key cytokine secreted during viral infections, and overlapped them with known GD-associated SNPs. We mapped an open chromatin region overlapping two adjacent GD-associated SNPs (rs12101255 and rs12101261) in intron 1 of the thyroid stimulating hormone receptor (TSHR) gene. We then demonstrated that this region functions as a regulatory element through binding of the transcriptional repressor promyelocytic leukemia zinc finger protein (PLZF) at the rs12101261...
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abstractGraves disease (GD) is an autoimmune condition caused by interacting genetic and environmental factors. Genetic studies have mapped several single-nucleotide polymorphisms (SNPs) that are strongly associated with GD, but the mechanisms by which they trigger disease are unknown. We hypothesized that epigenetic modifications induced by microenvironmental influences of cytokines can reveal the functionality of GD-associated SNPs. We analyzed genome-wide histone H3 lysine 4 methylation and gene expression in thyroid cells induced by IFNα, a key cytokine secreted during viral infections, and overlapped them with known GD-associated SNPs. We mapped an open chromatin region overlapping two adjacent GD-associated SNPs (rs12101255 and rs12101261) in intron 1 of the thyroid stimulating hormone receptor (TSHR) gene. We then demonstrated that this region functions as a regulatory element through binding of the transcriptional repressor promyelocytic leukemia zinc finger protein (PLZF) at the rs12101261...
doi10.1073/pnas.1408821111
pmid25122677
date2014-08-26