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DNA methylation and Yin Yang‐1 repress adenosine A 2A receptor levels in human brain
Author(s) -
Buira Sandra P.,
Dentesano Guido,
Albasanz José Luis,
Moreno Jesús,
Martín Mairena,
Ferrer Isidre,
Barrachina Marta
Publication year - 2010
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2010.06928.x
Subject(s) - biology , dna methylation , microbiology and biotechnology , human brain , medicine , endocrinology , gene expression , genetics , gene , neuroscience
J. Neurochem. (2010) 115 , 283–295. Abstract 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.