title: Genome-wide mapping of Myc binding and gene regulation in serum-stimulated fibroblasts.
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.
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology, IFOM-IEO Campus, Milan, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Perna
authors.forename: G
authors.initials: G
authors.lastname: Fagà
authors.forename: A
authors.initials: A
authors.lastname: Verrecchia
authors.forename: M M
authors.initials: MM
authors.lastname: Gorski
authors.forename: I
authors.initials: I
authors.lastname: Barozzi
authors.forename: V
authors.initials: V
authors.lastname: Narang
authors.forename: J
authors.initials: J
authors.lastname: Khng
authors.forename: K C
authors.initials: KC
authors.lastname: Lim
authors.forename: W-K
authors.initials: WK
authors.lastname: Sung
authors.forename: R
authors.initials: R
authors.lastname: Sanges
authors.forename: E
authors.initials: E
authors.lastname: Stupka
authors.forename: T
authors.initials: T
authors.lastname: Oskarsson
authors.forename: A
authors.initials: A
authors.lastname: Trumpp
authors.forename: C-L
authors.initials: CL
authors.lastname: Wei
authors.forename: H
authors.initials: H
authors.lastname: Müller
authors.forename: B
authors.initials: B
authors.lastname: Amati
mesh_terms: D000818:Animals; D002460:Cell Line; D002874:Chromosome Mapping; D005347:Fibroblasts / Q000378:metabolism*; D005786:Gene Expression Regulation; D051379:Mice; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D044967:Serum / Q000502:physiology*
chemical_list: D016271:Proto-Oncogene Proteins c-myc