Elucidating altered transcriptional programs
Genetic mutations in genes involved in epigenetic-mediated mechanisms of gene regulation have been found in a broad array of solid tumors and hematologic malignancies.
Each of these components of epigenetic information has been found to play a critical role in cancer.
Furthermore, gene expression data contains valuable directional information indicated by arrows next to the gene expression data utilized by URA (blue), which incorporates hierarchical systems biology networks.
The core analysis of the workflow includes multi-omics data integration between chromatin binding and differential gene expression events The combination of both transcriptomic and epigenomic profiling offers insight into different levels of gene regulation, transcription factor binding motifs, DNA and chromatin modifications, and how each component is coupled to a functional output.
The intersection of analysis of motif enrichment (AME) and transcription factor target (TFT), and upstream regulator analysis (URA) approaches provides insights into cooperative networks of transcription factors associated with epigenomic regulators.
We propose a workflow for the genome-wide identification of epigenomic and transcriptional cooperation to elucidate transcriptional networks in cancer.The epigenomic effector network is regulated by chromatin binding or chromatin modification events resulting in gene expression changes.b Concerted analysis of chromatin immunoprecipitation Ch IP-Seq and RNA-Seq data (or similar data) enables identification of epigenomic and transcriptomic master regulators and transcription factor networks.These genetic mutations occur in a great variety of epigenetic enzymes, such DNA methyltransferases (DNMT3A/B) and hydroxymethyltransferases (TET1/2), but also to epigenetic readers and writers (Polycomb-group proteins), and erasers of histone modifications (histone demethylases).Another important area of investigation within the CE Program is elucidating the mechanisms by which epigenetic regulators orchestrate transcriptional programs in response to growth factor signaling and hormones and how such functional crosstalk is altered in cancer.
Search for elucidating altered transcriptional programs:
The discovered network is tightly connected and surrounds the histone lysine demethylase KDM3A, basic helix-loop-helix factors MYC, HIF1A, and SREBF1, as well as differentiation factors AP1, MYOD1, SP1, MEIS1, ZEB1, and ELK1.