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https://hdl.handle.net/1822/41029
Título: | Methylation at the CpG island shore region upregulates Nr3c1 promoter activity after early-life stress |
Autor(es): | Bockmühl, Yvonne Patchev, Alexandre V. Madejska, Arleta Hoffmann, Anke Sousa, João Carlos Sousa, Nuno Holsboer, Florian Almeida, Osborne F. X. Spengler, Dietmar |
Palavras-chave: | CpG island shore DNA methylation Early-life stress Glucocorticoid receptor Insulator Yin Yang |
Data: | Mar-2015 |
Editora: | Taylor and Francis |
Revista: | Epigenetics |
Citação: | Bockmühl, 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 |
Resumo(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. |
Tipo: | Artigo |
URI: | https://hdl.handle.net/1822/41029 |
DOI: | 10.1080/15592294.2015.1017199 |
ISSN: | 1559-2294 |
Versão da editora: | http://www.tandfonline.com/doi/abs/10.1080/15592294.2015.1017199 |
Arbitragem científica: | yes |
Acesso: | Acesso aberto |
Aparece nas coleções: | ICVS - Artigos em revistas internacionais / Papers in international journals |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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bockmuhl et al, 2015.pdf | 783,5 kB | Adobe PDF | Ver/Abrir |