[1]李周儒,刘捷,雷宇,等.组蛋白高乙酰化介导的Egr-1结合促进gdnf基因高转录[J].南方医科大学学报,2015,(05):697.
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组蛋白高乙酰化介导的Egr-1结合促进gdnf基因高转录()
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《南方医科大学学报》[ISSN:1673-4254/CN:44-1627/R]

卷:
期数:
2015年05期
页码:
697
栏目:
出版日期:
2015-05-15

文章信息/Info

Title:
Increased Egr-1 binding to promoter induced by histone hyperacetylation promotes gdnf
gene transcription
作者:
李周儒刘捷雷宇倪海波蔡红星张宝乐
关键词:
gdnf启动子组蛋白乙酰化Egr-1胶质瘤
Keywords:
gdnf promoter histone acetylation Egr-1 glioma
摘要:
目的探讨大鼠C6 胶质瘤细胞中gdnf 基因启动子II 区组蛋白H3K9 高乙酰化引发该基因高转录的机制。方法采用
ChIP-PCR技术检测了大鼠C6星形胶质瘤细胞和正常星形胶质细胞中gdnf基因启动子II区转录因子Egr-1结合位点处H3K9
的乙酰化水平以及Egr-1与该启动子的结合能力;利用Real-time PCR和ChIP-PCR技术,检测了组蛋白乙酰基转移酶抑制剂姜
黄素(Curcumin)和去乙酰化酶抑制剂曲古抑菌素A(TSA)处理对C6 胶质瘤细胞中gdnf 基因启动子II 区Egr-1 结合位点处
H3K9的乙酰化水平、Egr-1与之的结合能力以及该基因转录水平的影响。结果较之正常星形胶质细胞,C6胶质瘤细胞中gdnf
基因启动子II 区Egr-1 结合位点处H3K9 的乙酰化水平显著升高,并且Egr-1 与之的结合能力也显著升高(P<0.01)。当
Curcumin显著降低了Egr-1结合位点处H3K9乙酰化水平时,Egr-1与启动子II区的结合量以及gdnf基因mRNA的表达量都显
著下调(P<0.05);而当TSA显著升高了Egr-1 结合位点处H3K9 乙酰化水平时,Egr-1 与启动子II 区的结合量以及gdnf 基因
mRNA的表达量都显著升高(P<0.05)。结论在大鼠C6胶质瘤细胞中gdnf基因启动子II区H3K9高乙酰化介导的Egr-1结合
量升高可能是其高转录的原因。
Abstract:
Objective To 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. Methods The
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. Results Compared 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). Conclusion H3K9 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.

相似文献/References:

[1]周林,宗璐,张璐璐,等.GABRB2基因启动子区单核苷酸多态性与精神分裂症的关联[J].南方医科大学学报,2015,(02):256.

更新日期/Last Update: 1900-01-01