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DNA methylation and Yin Yang-1 repress adenosine A2A receptor levels in human brain

AuthorsBuira, Sandra P.; Dentesano, Guido ; Albasanz, José Luis; Moreno, Jesús; Martín, Mairena; Ferrer, Isidre; Barrachina, Marta
Issue Date2010
PublisherInternational Society for Neurochemistry
CitationJournal of Neurochemistry 115(1): 283-295 (2010)
AbstractAdenosine A2A receptors (A2ARs) are G-protein coupled receptors that stimulate adenylyl cyclase activity. The most A 2ARs-enriched brain region is the striatum, in which A2ARs are largely restricted to GABAergic neurons of the indirect pathway. We recently described how DNA methylation controls basal A2AR expression levels in human cell lines. The present report provides clues about the molecular mechanisms that promote human brain region-specific A2AR 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 2AR levels in the two cerebral regions. © 2010 International Society for Neurochemistry.
Identifiersdoi: 10.1111/j.1471-4159.2010.06928.x
issn: 0022-3042
e-issn: 1471-4159
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