ObjectiveTo study the regulation role and mechanism of protein acetylation on the expression of glioblastoma-derived neurotrophic factor (GDNF) in human glioma.MethodsSix normal brain tissue samples, six low-grade glioma brain tissue (LG-glioma), and six high-grade glioma brain tissue (HG-glioma) were collected for study. Human glioma U251 cells were treated with histone acetylase inhibitor and histone deacetylase inhibition. The mRNA level ofGDNFin glioma and normal controls was detected by Real-time PCR. H3K9 acetylation level of cAMP-response element binding protein (CREB) binding region on GDNF promoter and the ability of CREB combining toGDNFpromoter were detected by ChIP-PCR. The effects of histone acetylase and deacetylase inhibitors on transcription factor binding ability and GDNF expression were detected.ResultsThe mRNA level ofGDNFin HG-glioma was significantly higher than those in normal brain tissue and LG-glioma (P< 0.01). the h3k9 acetylation level ofGDNFpromoter region in the glioma was increased compared to that in the normal brain tissue (P< 0.01), and the acetylation level in creb-binding region on theGDNFpromoter was higher than that in the non-CREB-binding region (P< 0.01). the binding activity of creb andGDNFpromoter in HG-glioma was higher than those in normal brain tissue and LG-glioma (P< 0.05). after treatment of u251 cells with histone acetyltransferase inhibition, the level of acetylation in creb-binding region onGDNFpromoter, the binding activity of CREB andGDNFpromoter was decreased, andGDNFtranscription and expression were down-regulated, while histone deacetylase inhibitors had the opposite effect (P< 0.01).ConclusionHistone acetylation promotes the transcription expression ofGDNFin glioma by promoting the binding of transcription factor CREB to the promoter region of GDNF gene.
