Egr-1 and RNA POL II facilitate glioma cell GDNF transcription induced by histone hyperacetylation in promoter II
| Autor: | Xiao-He Gu, Ruiqin Yao, Guang-Quan Ji, Bao-Le Zhang, Dianshuai Gao, Ting-Wen Guo, Yu-Qi Shao, Le-Le Gao |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Egr-1 Transcription Genetic animal diseases Cell RNA polymerase II Biology Transfection Histones 03 medical and health sciences Transcription (biology) Cell Line Tumor Glial cell line-derived neurotrophic factor medicine Animals Humans Glial Cell Line-Derived Neurotrophic Factor Binding site Promoter Regions Genetic Gene Early Growth Response Protein 1 urogenital system Brain Neoplasms histone acetylation Acetylation Histone acetyltransferase Glioma Molecular biology GDNF Rats body regions 030104 developmental biology Histone medicine.anatomical_structure Oncology nervous system biology.protein RNA POL II RNA Polymerase II hormones hormone substitutes and hormone antagonists Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | The specific mechanisms for epigenetic regulation of gene transcription remain to be elucidated. We previously demonstrated that hyperacetylation of histone H3K9 in promoter II of glioma cells promotes high transcription of the glial cell line-derived neurotrophic factor (GDNF) gene. This hyperacetylation significantly enhanced Egr-1 binding and increased the recruitment of RNA polymerase II (RNA POL II) to that region (P < 0.05). Egr-1 expression was abnormally increased in C6 glioma cells. Further overexpression of Egr-1 significantly increased Egr-1 binding to GDNF promoter II, while increasing RNA POL II recruitment, thus increasing GDNF transcription (P < 0.01). When the acetylation of H3K9 in the Egr-1 binding site was significantly reduced by the histone acetyltransferase (HAT) inhibitor curcumin, binding of Egr-1 to GDNF promoter II, RNA POL II recruitment, and GDNF mRNA expression were significantly downregulated (P < 0.01). Moreover, curcumin attenuated the effects of Egr-1 overexpression on Egr-1 binding, RNA POL II recruitment, and GDNF transcription (P < 0.01). Egr-1 and RNA POL II co-existed in the nucleus of C6 glioma cells, with overlapping regions, but they were not bound to each other. In conclusion, highly expressed Egr-1 may be involved in the recruitment of RNA POL II in GDNF promoter II in a non-binding manner, and thereby involved in regulating GDNF transcription in high-grade glioma cells. This regulation is dependent on histone hyperacetylation in GDNF promoter II. |
| Databáze: | OpenAIRE |
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