Please use this identifier to cite or link to this item: http://hdl.handle.net/1822/41029

TitleMethylation at the CpG island shore region upregulates Nr3c1 promoter activity after early-life stress
Author(s)Bockmühl, Yvonne
Patchev, Alexandre V.
Madejska, Arleta
Hoffmann, Anke
Sousa, João Carlos
Sousa, Nuno
Holsboer, Florian
Almeida, Osborne F. X.
Spengler, Dietmar
KeywordsCpG island shore
DNA methylation
Early-life stress
Glucocorticoid receptor
Insulator
Yin Yang
Issue dateMar-2015
PublisherTaylor & Francis
JournalEpigenetics
CitationBockmühl, Y., Patchev, A. V., Madejska, A., Hoffmann, A., Sousa, J. C., Sousa, N., et. al.(2015). Methylation at the CpG island shore region upregulates Nr3c1 promoter activity after early-life stress. Epigenetics, 10(3), 247-257
Abstract(s)Early-life stress (ELS) induces long-lasting changes in gene expression conferring an increased risk for the development of stress-related mental disorders. Glucocorticoid receptors (GR) mediate the negative feedback actions of glucocorticoids (GC) in the paraventricular nucleus (PVN) of the hypothalamus and anterior pituitary and therefore play a key role in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis and the endocrine response to stress. We here show that ELS programs the expression of the GR gene (Nr3c1) by site-specific hypermethylation at the CpG island (CGI) shore in hypothalamic neurons that produce corticotropin-releasing hormone (Crh), thus preventing Crh upregulation under conditions of chronic stress. CpGs mapping to the Nr3c1 CGI shore region are dynamically regulated by ELS and underpin methylation-sensitive control of this region's insulation-like function via Ying Yang 1 (YY1) binding. Our results provide new insight into how a genomic element integrates experience-dependent epigenetic programming of the composite proximal Nr3c1 promoter, and assigns an insulating role to the CGI shore.
Typearticle
URIhttp://hdl.handle.net/1822/41029
DOI10.1080/15592294.2015.1017199
ISSN1559-2294
Publisher versionhttp://www.tandfonline.com/doi/abs/10.1080/15592294.2015.1017199
Peer-Reviewedyes
AccessopenAccess
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

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