CACGTG

CACGTG is a hexanucleotide DNA sequence that is palindromic and serves as a high-affinity binding site for basic helix-loop-helix transcription factors. It is the canonical high-affinity E-box variant within the broader CANNTG E-box family.

Binding: The motif is recognized by heterodimers of bHLH proteins such as Myc/Max, Mad/Max, and USF1/USF2, among others. Binding typically occurs as a dimer to palindromic CACGTG sequences in promoters and enhancers, modulating transcription. In many contexts, CACGTG-containing E-boxes are among the strongest DNA-protein interaction sites, contributing to robust transcriptional responses.

Genomic context and function: CACGTG is enriched in regulatory regions controlling genes involved in cell growth, metabolism, and differentiation. Myc-driven transcriptional programs commonly rely on E-box binding to upregulate genes supporting ribosome biogenesis and metabolism; dysregulation is linked to oncogenesis.

Methylation and regulation: The motif contains a CpG dinucleotide; cytosine methylation within CACGTG can alter transcription factor binding and gene expression, with methylation generally reducing affinity for certain bHLH factors, though effects vary by factor and context.

Taxonomy and evolution: The CACGTG motif is conserved across vertebrates and is a well-studied element in promoter analysis and gene regulation. It is used in experimental and computational annotation of regulatory regions as part of E-box motif catalogs.