Overall, hypermethylation of promoter regions had a negative impact on gene expression, as the median expression of genes at non-hypermethylated promoters bound by MYCN was 2.6 fold higher than hypermethylated promoters bound by MYCN . The median expression of genes with non-hypermethylated promoters that were bound by MYCN was ,2.8-fold higher than similar promoters occupied by MeCP2 , consistent with MYCN having a Gefitinib EGFR/HER2 inhibitor positive impact on transcription. Overall, the median expression of genes with non-hypermethylated promoters and co-localization of MYCN and MeCP2 was intermediate between those occupied only by MYCN or MeCP2 , indicating that MeCP2 interaction with MYCN can moderate gene expression. Interestingly, there was no difference in median expression for MeCP2 bound promoters that were non-hypermethylated versus those that were hypermethylated ; consistent with the hypothesis that MeCP2 binding in the absence of hypermethylation can have a suppressive effect. However, its repressive effects appear greater when associated with hypermethylated CpG islands within promoters relative to MeCP2 binding within promoters which do not contain CpG islands . Among hypermethylated CpG island promoters, median gene expression was 3.4-fold higher for those co-occupied by MYCN and MeCP2 relative to those promoters only bound by MeCP2 , providing evidence that MYCN interaction can moderate the repressive effects of MeCP2. No other statistically significant difference in median gene expression was detected among the comparisons made . We conclude that MeCP2 has an overall negative impact on gene expression, while MYCN has a more positive influence. In addition, interaction of MYCN with MeCP2 appears to mitigate the negative effects of MeCP2 on gene expression, particularly at promoter regions containing CpG islands. In order to determine if there might be higher order functional differences between genes with promoters uniquely bound by MYCN or MeCP2 or jointly bound by both proteins, analysis of these gene subsets was carried out using Ingenuity Pathway Analysis software. The top 5 enrichment categories for genes uniquely bound by MYCN included cellular movement, cell death, gene expression, cell cycle and cell signaling, all terms which might be expected based on numerous prior studies of MYCN . Although these terms were most Y-27632 dihydrochloride customer reviews significantly enriched for genes uniquely bound by MYCN, they were also moderately enriched for genes uniquely bound by MeCP2 or cobound by MYCN/MeCP2 .