The 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. Â© 2012 Macmillan Publishers Limited All rights reserved.
|Titolo:||Genome-wide mapping of Myc binding and gene regulation in serum-stimulated fibroblasts|
|Autori:||Perna, D.; Fagà, 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.; Müller, H.; Amati, B.|
|Data di pubblicazione:||2012|
|Digital Object Identifier (DOI):||10.1038/onc.2011.359|
|Appare nelle tipologie:||1.1 Journal article|