ork is the first to examine genome-wide analysis of DNA methylation in uterine leiomyoma and there are no existing data against which we can compare our results, “7901789 our mRNA expression profiles 
are consistent with previously published reports. In our genome-wide analysis, we observed that 1,031 transcriptional regulatory regions were differentially methylated and only 525 mRNA species were transcriptionally altered in uterine leiomyoma compared with myometrial tissue. This degree of mismatch between DNA methylation and steady-state mRNA GW 501516 levels was expected since changes in DNA methylation may not always lead to changes in steady-state mRNA levels for the following potential reasons. DNA methylation alone may not be sufficient to alter mRNA expression, and other events such as changes in the structure of chromatin formed on a methylated template are needed to render it transcriptionally altered. The availability and binding capacity of specific transcription factors are needed to regulate the rate of mRNA transcription from a gene promoter. Finally, other factors that regulate the half-life of a certain transcript will determine its steady-state levels. Consequently, it is expected that changes in steady-state mRNA levels are regulated only partially by DNA methylation. Although, we attempted to account for differences in the menstrual cycle, the majority of the samples included in our analysis were obtained during the proliferative phase. Moreover, it is challenging to date the endometrium for cycle phase since many women with uterine leiomyomas have irregular cycles with prolonged bleeding. The small number of secretory phase samples did not permit us to compare biological differences as a function of the cycle phase. Since the correlation between differences in DNA methylation and gene expression was evaluated in paired samples from the same patient, the effect of cycle phase on this analysis was further minimized. In this study, we noted a key epigenetic mechanism whereby increased promoter methylation leads to transcriptional suppression in uterine leiomyoma compared with matched normal myometrial tissues. The second predominant mechanism was hypomethylation associated with overexpression of genes indicating an overall inverse relationship between DNA methylation and gene expression in uterine leiomyoma. However, we also observed some genes to be hypermethylated and upregulated, and other genes to be hypomethylated and downregulated. The absence of an inverse relationship between promoter DNA methylation and mRNA expression in this minor group of genes is consistent with previously published data. For example, methylation of one particular CpG island in the NR5A1 gene is associated with transcriptional suppression, whereas methylation of another CpG island located 4 kb downstream is associated with overexpression of NR5A1 mRNA. It is conceivable that the effects of a single methylated CpG island on gene expression may be either gene-specific or location-specific within the same gene. We verified the “9357531 effects of promoter DNA methylation on transcriptional inhibition of three tumor suppressor genes namely, KLF11, DLEC1, and KRT19. KLF11 is a transcription factor and a member of the transforming growth factor beta family, which is involved in key cellular functions such as apoptosis, proliferation, and differentiation. KLF11 is expressed in a number of human tissues, and it is repressed in several human cancers. It inhibits neoplastic tran
