Gene Set: FERNANDEZ_BOUND_BY_MYC

Standard name FERNANDEZ_BOUND_BY_MYC
Systematic name M3456
Brief description Genes identified by ChIP within the high-affinity group of MYC [GeneID=4609] targets.
Full description or abstract The transcription factor Myc is induced by mitogenic signals and regulates downstream cellular responses. If overexpressed, Myc promotes malignant transformation. Myc modulates expression of diverse genes in experimental systems, but few are proven direct targets. Here, we present a large-scale screen for genomic Myc-binding sites in live human cells. We used bioinformatics to select consensus DNA elements (CACGTG or E-boxes) situated in the 5' regulatory region of genes and measured Myc binding to those sequences in vivo by quantitative chromatin immunoprecipitation. Strikingly, most promoter-associated E-boxes showed selective recovery with Myc, unlike non-E-box promoters or E-boxes in bulk genomic DNA. Promoter E-boxes were distributed in two groups bound by Myc at distinct frequencies. The high-affinity group included an estimated 11% of all cellular loci, was highly conserved among different cells, and was bound independently of Myc expression levels. Overexpressed Myc associated at increased frequency with low-affinity targets and, at extreme levels, also with other sequences, suggesting that some binding was not sequence-specific. The strongest DNA-sequence parameter defining high-affinity targets was the location of E-boxes within CpG islands, correlating with an open, preacetylated state of chromatin. Myc further enhanced histone acetylation, with or without accompanying induction of mRNA expression. Our findings point to a high regulatory and biological diversity among Myc-target genes.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 12695333   Authors: Fernandez PC,Frank SR,Wang L,Schroeder M,Liu S,Greene J,Cocito A,Amati B
Exact source Table 1
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Organism Homo sapiens
Contributed by Yujin Hoshida (Broad Institute)
Source platform HUMAN_GENE_SYMBOL
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Version history 3.0: Renamed from FERNANDEZ_MYC_TARGETS

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