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.