Perna, D.Faga, G.Verrecchia, A.Gorski, M. M.Barozzi, I.Narang, V.Khng, J.Lim, K. C.Sung, W.-K.Sanges, R.Stupka, E.Oskarsson, T.Trumpp, A.Wei, C.-L.Mueller, H.Amati, B.2012-04-262012-04-262012-04-26201210.1038/onc.2011.359https://infoscience.epfl.ch/handle/20.500.14299/79696WOS:000302231400008The transition from quiescence to proliferation is a key regulatory step that can be induced by serum stimulation in cultured fibroblasts. The transcription factor Myc is directly induced by serum mitogens and drives a secondary gene expression program that remains largely unknown. Using mRNA profiling, we identify close to 300 Myc-dependent serum response (MDSR) genes, which are induced by serum in a Myc-dependent manner in mouse fibroblasts. Mapping of genomic Myc-binding sites by ChIP-seq technology revealed that most MDSR genes were directly targeted by Myc, but represented a minor fraction (5.5%) of all Myc-bound promoters (which were 22.4% of all promoters). Other target loci were either induced by serum in a Myc-independent manner, were not significantly regulated or were negatively regulated. MDSR gene products were involved in a variety of processes, including nucleotide biosynthesis, ribosome biogenesis, DNA replication and RNA control. Of the 29 MDSR genes targeted by RNA interference, three showed a requirement for cell-cycle entry upon serum stimulation and 11 for long-term proliferation and/or survival. Hence, proper coordination of key regulatory and biosynthetic pathways following mitogenic stimulation relies upon the concerted regulation of multiple Myc-dependent genes. Oncogene (2012) 31, 1695-1709; doi:10.1038/onc.2011.359; published online 22 August 2011MycchromatintranscriptionserumEmbryonic Stem-CellsC-MycTranscription FactorIn-VivoChromatin-StructureCycle ProgressionProtein-SynthesisDna-ReplicationNuclear ImportRna Exosometext::journal::journal article::research article