(a) Specific-gene regulation: Based on the study and structural elucidation of
the Enhancerbox (E-box) binding by MYC, specific MYC-induced target genes were
discovered and characterized. (b) Global gene activation: Genome-wide chromatin
immunoprecipitation sequencing (ChIP-seq) studies of MYC identified that MYC
binds at the promoters of most RNA polymerase II (Pol II)-bound and expressed
genes. Accordingly, Myc induces a global increase in cellular mRNA levels in
some biological systems. (c) Gene-specific affinity: Although MYC binding is
detectable at most promoters, promoter affinities for MYC differ widely. Genes
with high promoter–MYC affinity are bound and upregulated by MYC at
physiological levels, but are not further induced at oncogenic levels, as
binding is already saturated. Instead, oncogenic MYC upregulates low affinity
target genes. The affinity model can reconcile the seemingly opposing specific
gene and global gene models. Green arrows indicate activation, red arrow
indicates repression and grey arrows indicate no regulation of genes. RPL8, 60S
ribosomal protein L8; VEGFA, vascular endothelial growth factor A.