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

D. Perna, G. Fagà, A. Verrecchia, M. M. Gorski, I. Barozzi, V. Narang, J. Khng, K. C. Lim, W. K. Sung, R. Sanges, E. Stupka, T. Oskarsson, A. Trumpp, C. L. Wei, H. Müller, B. Amati

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1695-1709
Number of pages15
JournalOncogene
Volume31
Issue number13
DOIs
Publication statusPublished - Mar 29 2012

Keywords

  • chromatin
  • Myc
  • serum
  • transcription

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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