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

By 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 and B. Amati

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. © 2012 Macmillan Publishers Limited All rights reserved

Topics: chromatin, Myc, serum, transcription, Animals, Cell Line, Fibroblasts, Mice, Proto-Oncogene Proteins c-myc, Serum, Chromosome Mapping, Gene Expression Regulation, Molecular Biology, Genetics, Cancer Research
Year: 2012
DOI identifier: 10.1038/onc.2011.359
OAI identifier: oai:iris.sissa.it:20.500.11767/68494
Provided by: SISSA Digital Library
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