ChIP-chip from mouse embryonic stem (mES) cells

c-Myc (Myc) is an important transcriptional regulator in embryonic stem (ES) cells, somatic cell reprogramming, and cancer, yet functionally differs from the core pluripotency transcription factors, such as Oct4, Sox, and Nanog. Here, we identify a Myc-centered regulatory network in ES cells by combining protein-protein interaction and protein-DNA interaction studies, and show that Myc interacts with the NuA4 histone acetyltransferase complex, previously identified as a critical regulator in ES cell identity. In combination with previously studied transcriptional regulatory network information, we construct three ES cell modules (Core, Polycomb, and Myc) and show that these modules are functionally separable in ES, iPS, MEFs, and partial iPS cells, suggesting that the overall ES cell transcription program is comprised of distinct functional units. With these regulatory modules as an analytical tool, we have reassessed data suggesting that cancer cells reactivate an ES cell-like transcriptional program. We find that the Myc module, independent of the Core module, is active in various cancers and predicts cancer outcome. These observations argue against the hypothesis linking an embryonic gene expression signature with cancer or cancer stem cells. The apparent similarity of cancer and ES cell signatures reflects in large part the pervasive nature of Myc regulatory network. Keywords: Biotin-mediated Chip-chip, Antibody ChIP-chip, Mouse embryonic stem cells