Genome-wide Mapping of Myc Binding and Gene Regulation in Serum-stimulated Fibroblasts

Overview

Journal Oncogene

Specialties Molecular Biology
Oncology

Date 2011 Aug 24

PMID 21860422

Citations 64

Authors

D Perna

G Faga

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 Muller

B Amati

Affiliations

Soon will be listed here.

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.

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