DNA methylation and Yin Yang-1 repress adenosine A2A receptor levels in human brain.
J Neurochem
; 115(1): 283-95, 2010 Oct.
Article
em En
| MEDLINE
| ID: mdl-20666933
Adenosine A(2A) receptors (A(2A) Rs) are G-protein coupled receptors that stimulate adenylyl cyclase activity. The most A(2A) Rs-enriched brain region is the striatum, in which A(2A) Rs are largely restricted to GABAergic neurons of the indirect pathway. We recently described how DNA methylation controls basal A(2A) R expression levels in human cell lines. The present report provides clues about the molecular mechanisms that promote human brain region-specific A(2A) R gene (ADORA2A) basal expression. The transcription factors ZBP-89 and Yin Yang-1 (YY1) have been characterized as regulators of ADORA2A in SH-SY5Y cells by means of specific expression vectors/siRNAs transient transfection and chromatin immunoprecipitation assay. ZBP-89 plays a role as an activator and YY1 as a repressor. No differences were found in ZBP-89 levels with western blot between the putamen and cerebellum of human postmortem brains. However, increased YY1 levels and DNA methylation percentage in the 5' untranslated region of ADORA2A, using SEQUENOM MassArray, were found in the cerebellum with respect to the putamen of human brains, showing an inverse relationship with A(2A) R levels in the two cerebral regions.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Química Encefálica
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Metilação de DNA
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Receptor A2A de Adenosina
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Fator de Transcrição YY1
Limite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article