Global identification of Myc target genes reveals its direct role in mitochondrial biogenesis and its E-box usage in vivo

The Myc oncoprotein is a transcription factor involved in a variety of human cancers. Overexpression of Myc is associated with malignant transformation. In normal cells, Myc is induced by mitotic signals, and in turn, it regulates the expression of downstream target genes. Although diverse roles of...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2008-03, Vol.3 (3), p.e1798-e1798
Main Authors: Kim, Jonghwan, Lee, Ji-hoon, Iyer, Vishwanath R
Format: Article
Language:English
Subjects:
Analysis
Biosynthesis
Cancer
Cell cycle
Chromatin
Chromatin Immunoprecipitation
Coding
Deoxyribonucleic acid
DNA
Fibroblasts
Gene expression
Genes
Genes, myc
Genetic transformation
Genetics and Genomics/Cancer Genetics
Genetics and Genomics/Gene Function
Genomes
HeLa Cells
Humans
Immunoprecipitation
In vivo methods and tests
Ligase Chain Reaction
Mammals
Mitochondria
Mitochondrial DNA
Molecular biology
Molecular Biology/Transcription Initiation and Activation
Myc protein
Oligonucleotide Array Sequence Analysis
Ontology
Physiology
Promoters
Promoters (Genetics)
Proteins
Respiration
Synthetic biology
Target recognition
Transcription factors
Transformation
Tumors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The Myc oncoprotein is a transcription factor involved in a variety of human cancers. Overexpression of Myc is associated with malignant transformation. In normal cells, Myc is induced by mitotic signals, and in turn, it regulates the expression of downstream target genes. Although diverse roles of Myc have been predicted from many previous studies, detailed functions of Myc targets are still unclear. By combining chromatin immunoprecipitation (ChIP) and promoter microarrays, we identified a total of 1469 Myc direct target genes, the majority of which are novel, in HeLa cells and human primary fibroblasts. We observed dramatic changes of Myc occupancy at its target promoters in foreskin fibroblasts in response to serum stimulation. Among the targets of Myc, 107 were nuclear encoded genes involved in mitochondrial biogenesis. Genes with important roles in mitochondrial replication and biogenesis, such as POLG, POLG2, and NRF1 were identified as direct targets of Myc, confirming a direct role for Myc in regulating mitochondrial biogenesis. Analysis of target promoter sequences revealed a strong preference for Myc occupancy at promoters containing one of several described consensus sequences, CACGTG, in vivo. This study thus sheds light on the transcriptional regulatory networks mediated by Myc in vivo.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0001798