Delineation of Methyl-DNA Binding Protein Interactions in the Prostate Cancer Genome

The purpose of this study is to generate a genome-wide association profile of Methyl-CpG Domain-containing (MBD) proteins, such as MeCP2, MBD1, MBD2 and MBD4, in malignant prostate cancer cells and matched normal or benign prostate cells using Chromatin Immunoprecipitation followed by Next Generation Sequencing (ChIP-Seq). The preliminary ChIP-Seq results establish the proof-of-principle that ChIP-Seq can be performed using the limited amounts of material available from these clinical samples (biopsies). This is the most significant result to date because it suggests that this study will be able to generate novel databases identifying the genome-wide MBD association profiles using clinical samples. In addition, our preliminary ChIP-Seq results have identified interesting genes such as a histone demethylase, a tetrahydrofolate synthase and piR-61309 near the association sites of MBD family members. In parallel, RNA expression profiles from the same tissues were generated to allow comparison of differential patterns of gene expression with differential patterns of MBD protein association. Microarray analysis has been performed and has identified genes that are up-regulated and down-regulated by at least 2-fold in Stage 3 prostate cancer cells.
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