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Oncogene. 2012 Mar 29;31(13):1695-709. doi: 10.1038/onc.2011.359. Epub 2011 Aug 22.

Genome-wide mapping of Myc binding and gene regulation in serum-stimulated fibroblasts.

Author information

1
Department of Experimental Oncology, European Institute of Oncology, IFOM-IEO Campus, Milan, Italy.

Abstract

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.

PMID:
21860422
PMCID:
PMC3324106
DOI:
10.1038/onc.2011.359
[Indexed for MEDLINE]
Free PMC Article

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