Increased Egr-1 binding to promoter induced by histone hyperacetylation promotes gdnf gene transcription.
- Author:
Zhouru LI
1
;
Jie LIU
;
Yu LEI
;
Haibo NI
;
Hongxing CAI
;
Baole ZHANG
Author Information
- Publication Type:Journal Article
- MeSH: Acetylation; Animals; Astrocytes; metabolism; Binding Sites; Cell Line, Tumor; Early Growth Response Protein 1; metabolism; Glial Cell Line-Derived Neurotrophic Factor; genetics; Glioma; metabolism; Histones; chemistry; Promoter Regions, Genetic; Protein Processing, Post-Translational; RNA, Messenger; Rats; Transcription, Genetic
- From: Journal of Southern Medical University 2015;35(5):697-701
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the mechanism of high transcription of the glial cell-line derived neurotrophic factor (gdnf) gene induced by hyperacetylation of histone H3 lysine 9 (H3K9) at its promoter region II in rat C6 glioma cells.
METHODSThe acetylation level of H3K9 at Egr-1 binding site in gdnf gene promoter region II and the binding capacity of Egr-1 to its binding site in gdnf promoter were examined by ChIP-PCR in C6 astroglioma cells and normal rat astrocytes, and its changes were investigated in C6 astroglioma cells after treatment with histone acetyltransferase inhibitor curcumin or deacetylase inhibitor trichostatin A.
RESULTSCompared normal astrocytes, C6 astroglioma cells showed significantly increased acetylation level of H3K9 at Egr-1 binding site in gdnf gene promoter region II and Egr-1 binding capacity (P<0.01). Curcumin treatment significantly reduced H3K9 acetylation level at Egr-1 binding site and decreased both the binding of Egr-1 to promoter region II and gdnf mRNA levels in C6 astroglioma cells (P<0.05). Conversely, increased H3K9 acetylation at the Egr-1 binding site induced by trichostatin A significantly increased the binding of Egr-1 to promoter region II and gdnf mRNA expression levels (P<0.05).
CONCLUSIONH3K9 hyperacetylation induces increased Egr-1 binding to gdnf gene promoter II, which might be the reason for the high transcription level of gdnf gene in rat C6 glioma cells.