Analysis of Myc bound loci identified by CpG island arrays shows that Max is essential for Myc-dependent repression.
The c-myc proto-oncogene encodes a transcription factor, c-Myc, which is deregulated and/or overexpressed in many human cancers. Despite c-Myc's importance, the identity of Myc-regulated genes and the mechanism by which Myc regulates these genes remain unclear. By combining chromatin immunoprecipitation with CpG island arrays, we identified 177 human genomic loci that are bound by Myc in vivo. Analyzing a cohort of known and novel Myc target genes showed that Myc-associated protein X, Max, also bound to these regulatory regions. Indeed, Max is bound to these loci in the presence or absence of Myc. The Myc:Max interaction is essential for Myc-dependent transcriptional activation; however, we show that Max bound targets also include Myc-repressed genes. Moreover, we show that the interaction between Myc and Max is essential for gene repression to occur. Taken together, the identification and analysis of Myc bound target genes supports a model whereby Max plays an essential and universal role in the mechanism of Myc-dependent transcriptional regulation.
Ontario Cancer Institute/Princess Margaret Hospital, University of Toronto, Ontario M5G 2M9, Canada.
Daniel Y L
DY
Mao
John D
JD
Watson
Pearlly S
PS
Yan
Dalia
D
Barsyte-Lovejoy
Fereshteh
F
Khosravi
W Wei-Lynn
WW
Wong
Peggy J
PJ
Farnham
Tim H-M
TH
Huang
Linda Z
LZ
Penn
D018899:CpG Islands / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D005809:Genes, Regulator / Q000235:genetics; D016259:Genes, myc / Q000235:genetics*; D018922:HL-60 Cells; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D012097:Repressor Proteins