Fig. 4

Hypermethylated CRE in silencer II of GDNF promoter II promotes CREB-mediated high GDNF transcription in GBM cells. a The conserved CREB binding motif (MA0018.2) in human, mouse, and rat from JASPAR database. The gray box shows a CpG dinucleotide that is a DNA methylation-sensitive site. b CRE methylation in different cis-acting elements of GDNF promoter II in GBM (n = 3) and NB (n = 3) tissues as assessed by BSP. The black box indicates CpG methylation in CRE, black circles indicate methylated sites, and white circles indicate the unmethylated sites. c CRE methylation levels in GDNF enhancer II and silencer II in GBM and NB tissues (n = 3). d CRE methylation in different cis-acting elements of GDNF promoter II in U251, U343, and NHA cells as assessed by BSP (n = 5). e CRE methylation levels in GDNF enhancer II and silencer II in U251, U343, and NHA cells (n = 3). f Circular plasmids containing GDNF promoter II with different methylation patterns (n = 5). g Effect of CREB overexpression on the activity of GDNF promoter II with different methylation patterns (n = 3). All data are mean ± SD. ** and ## P < 0.01