Epioncogene Networks: Identification of Epigenomic and Transcriptomic Cooperation by Multi-omics Integration of ChIP-Seq and RNA-Seq Data

Abstract

Next generation sequencing and systems biology have changed our understanding of oncogenesis. Master regulators at the transcriptional and epigenomic level have the ability to affect how an entire network of cancer genes behaves, and thereby taking on an oncogenic role. Further, epigenetic factors cooperate and team up with transcription factors to control specific gene target networks. Transcriptomics in combination with epigenomic profiling and measurement of chromatin accessibility enables global detection of epigenetic modifications and characterization of transcriptional and epigenetic footprints. Chromatin remodelers and transcription factors are in close communication via recognition of posttranslational histone modifications, DNA methylation marks, and sequence motifs to coordinate dynamic exchange of chromatin between open transcriptionally active conformations and compacted silences ones. Integration of complementary high-throughput sequencing platforms (HiC, DNAseI-Seq, MNase-Seq, FAIRE-Seq, ATAC-Seq, ChIP-Seq, ChIA-PET, TBS-Seq, WGBS-Seq, RNA-Seq, GRID-Seq) including chromatin higher-order structures, DNase hypersensitive sites, chromatin accessibility, histone modification, chromatin binding, and DNA methylation enables identification of cooperation and gene target networks. In cancer, due to the ability to team up with transcription factors, epigenetic factors concert mitogenic and metabolic gene networks claiming the role of a cancer master regulators or epioncogenes.