title: Egr-1 participates in abnormally high gdnf gene transcription mediated by histone hyperacetylation in glioma cells.
abstract: Abnormally high transcription of the glial cell-line derived neurotrophic factor (gdnf) gene in glioma cells is related to the hyperacetylation of histone H3 lysine 9 (H3K9) in its promoter region II, but the mechanism remains unclear. There are three consecutive putative binding sites for the transcription factor early growth response protein 1(Egr-1) in promoter region II of the gdnf gene, and Egr-1 participates in gdnf gene transcription activation. Here we show that the acetylation level of H3K9 at Egr-1 binding sites in gdnf gene promoter region II in rat C6 astroglioma cells was significantly higher than that in normal astrocytes, and the binding capacity was also significantly higher. In C6 astroglioma cells, gdnf gene transcription significantly decreased after Egr-1 knock-down. In addition, the deletion or mutation of the Egr-1 binding site also significantly down-regulated the activity of promoter region II of this gene in vitro. When curcumin decreased the acetylation level of H3K9 at the Egr-1 binding site, the binding of Egr-1 to promoter region II and GDNF mRNA levels significantly decreased. In contrast, trichostatin A treatment significantly increased H3K9 acetylation at the Egr-1 binding site, which significantly increased both the binding of Egr-1 with promoter region II and GDNF mRNA levels. In this context, knocking down Egr-1 significantly reduced the elevation in gdnf gene transcription. Collectively, our results demonstrate that the hyperacetylation of H3K9 at Egr-1 binding sites in promoter region II of the gdnf gene can up-regulate the binding of Egr-1 to increase gdnf gene transcription in glioma cells.
authors.affiliation: Department of Neurobiology and Anatomy, Xuzhou Medical College, Xuzhou 221004, Jiangsu, China.
authors.forename: Bao-Le
authors.initials: BL
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu, China.
authors.forename: Hai-Bo
authors.initials: HB
authors.lastname: Ni
authors.affiliation: Department of Neurobiology and Anatomy, Xuzhou Medical College, Xuzhou 221004, Jiangsu, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Neurobiology and Anatomy, Xuzhou Medical College, Xuzhou 221004, Jiangsu, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Lei
authors.affiliation: Department of Neurobiology and Anatomy, Xuzhou Medical College, Xuzhou 221004, Jiangsu, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Neurobiology and Anatomy, Xuzhou Medical College, Xuzhou 221004, Jiangsu, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Department of Neurobiology and Anatomy, Xuzhou Medical College, Xuzhou 221004, Jiangsu, China.
authors.forename: Ruiqin
authors.initials: R
authors.lastname: Yao
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu, China.
authors.forename: Zheng-Quan
authors.initials: ZQ
authors.lastname: Yu
authors.affiliation: Department of Neurobiology and Anatomy, Xuzhou Medical College, Xuzhou 221004, Jiangsu, China. Electronic address: dshgao@vip.sina.com.
authors.forename: Dian-Shuai
authors.initials: DS
authors.lastname: Gao
mesh_terms: D000107:Acetylation; D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D051766:Early Growth Response Protein 1 / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D005910:Glioma / Q000235:genetics* / Q000378:metabolism*; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D051381:Rats
chemical_list: D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006657:Histones; D051548:Histone Acetyltransferases
keywords: Egr-1; GDNF; Glioma; Histone acetylation; Promoter