The study identifies genomic targets of the human c-Myc protein through a large-scale screen for Myc-binding sites in live human cells. Using bioinformatics, the researchers selected consensus DNA elements (CACGTG or E-boxes) in the 5' regulatory regions of genes and measured Myc binding in vivo via quantitative chromatin immunoprecipitation (ChIP). They found that 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 divided into two groups bound by Myc at distinct frequencies: a high-affinity group (11% of all cellular loci) that was highly conserved among different cells and bound independently of Myc expression levels, and a low-affinity group that showed increased binding with overexpressed Myc. The strongest parameter defining high-affinity targets was the location of E-boxes within CpG islands, which correlated with an open, preacetylated chromatin state. Myc also enhanced histone acetylation, with or without accompanying induction of mRNA expression. The findings suggest a high regulatory and biological diversity among Myc-target genes. The study also shows that Myc binds to a large number of genomic loci, indicating significant diversity in the transcriptional response. Myc-binding sites were conserved among different cell lines and primary cells, and the data reveal that promoter-associated E-boxes have different and characteristic affinities for Myc. Sequence analysis showed that Myc-target sites are enriched for CpG islands, which are associated with an open chromatin state. Myc binding to E-boxes was found to be influenced by chromatin structure and modifications, as well as other DNA-binding proteins. The study also shows that Myc can associate with non-E-box promoters, suggesting that some binding is not sequence-specific. Myc-target genes belong to diverse functional categories, including apoptosis, cell cycle, nucleolar function, ribosomal proteins and translation factors, growth factors, receptors, signal transduction, and so on. The study confirms and extends the possible involvement of Myc in diverse pathways, most notably energy, redox, and DNA metabolism. Myc also targets many genes encoding other transcription factors and nuclear regulators, suggesting that Myc is likely to participate in an extensive reprogramming of gene expression, both directly and through the action of other transcriptional regulators. The study highlights the importance of understanding the genomic targets of Myc, as it provides insights into the biological functions of Myc and its role in cellular physiology.The study identifies genomic targets of the human c-Myc protein through a large-scale screen for Myc-binding sites in live human cells. Using bioinformatics, the researchers selected consensus DNA elements (CACGTG or E-boxes) in the 5' regulatory regions of genes and measured Myc binding in vivo via quantitative chromatin immunoprecipitation (ChIP). They found that 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 divided into two groups bound by Myc at distinct frequencies: a high-affinity group (11% of all cellular loci) that was highly conserved among different cells and bound independently of Myc expression levels, and a low-affinity group that showed increased binding with overexpressed Myc. The strongest parameter defining high-affinity targets was the location of E-boxes within CpG islands, which correlated with an open, preacetylated chromatin state. Myc also enhanced histone acetylation, with or without accompanying induction of mRNA expression. The findings suggest a high regulatory and biological diversity among Myc-target genes. The study also shows that Myc binds to a large number of genomic loci, indicating significant diversity in the transcriptional response. Myc-binding sites were conserved among different cell lines and primary cells, and the data reveal that promoter-associated E-boxes have different and characteristic affinities for Myc. Sequence analysis showed that Myc-target sites are enriched for CpG islands, which are associated with an open chromatin state. Myc binding to E-boxes was found to be influenced by chromatin structure and modifications, as well as other DNA-binding proteins. The study also shows that Myc can associate with non-E-box promoters, suggesting that some binding is not sequence-specific. Myc-target genes belong to diverse functional categories, including apoptosis, cell cycle, nucleolar function, ribosomal proteins and translation factors, growth factors, receptors, signal transduction, and so on. The study confirms and extends the possible involvement of Myc in diverse pathways, most notably energy, redox, and DNA metabolism. Myc also targets many genes encoding other transcription factors and nuclear regulators, suggesting that Myc is likely to participate in an extensive reprogramming of gene expression, both directly and through the action of other transcriptional regulators. The study highlights the importance of understanding the genomic targets of Myc, as it provides insights into the biological functions of Myc and its role in cellular physiology.