DNA methylation and Yin Yang-1 repress adenosine A2A receptor levels in human brain.
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.
Buira
Sandra P
SP
Institut de Neuropatologia, Servei d'Anatomia Patològica, IDIBELL-Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Spain.
Dentesano
Guido
G
Albasanz
José Luis
JL
Moreno
Jesús
J
Martín
Mairena
M
Ferrer
Isidre
I
Barrachina
Marta
M
D020121:5' Untranslated Regions / Q000235:genetics; D000368:Aged; D001483:Base Sequence; D015153:Blotting, Western; D001923:Brain Chemistry / Q000502:physiology*; D002460:Cell Line; D002531:Cerebellum / Q000378:metabolism; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011699:Putamen / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D034741:RNA, Small Interfering / Q000235:genetics; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics; D014162:Transfection; D050986:YY1 Transcription Factor / Q000235:genetics*
D020121:5' Untranslated Regions; D004268:DNA-Binding Proteins; D034741:RNA, Small Interfering; D043705:Receptor, Adenosine A2A; D014157:Transcription Factors; D050986:YY1 Transcription Factor; C494698:YY1 protein, human; C110951:ZNF148 protein, human; D012313:RNA