Cellular cis-regulatory DNA elements (CREs)

Cellular cis-regulatory DNA elements (CREs) are non-coding genomic sequences, such as promoters, enhancers, silencers, and insulators, that regulate the transcription of genes located on the same DNA molecule (Wittkopp & Kalay, 2011). These elements serve as binding platforms for transcription factors and co-regulators, facilitating the recruitment of RNA polymerase II to specific gene loci to control the timing and level of protein production (NIH, 2023). Mutations or structural variations in CREs are significant drivers of human disease; for example, enhancer hijacking can lead to oncogene over-expression in cancer, while other non-coding mutations cause Mendelian disorders by disrupting tissue-specific regulatory control (Spielmann et al., 2018). Therapeutically, CREs are now being targeted using genome-editing technologies like CRISPR-Cas9 to treat conditions such as sickle cell disease by disrupting specific erythroid enhancers, such as the BCL11A enhancer (FDA, 2023). This approach allows for the precise modulation of gene expression levels without altering the primary protein-coding sequence, offering a novel paradigm for genetic medicine.

Other names

Cis-regulatory elementsCREsEnhancersPromotersSilencersInsulatorsRegulatory DNA sequencesNon-coding regulatory elements

Modulation of gene transcription through direct sequence modification to disrupt or create transcription factor binding sites, or via the recruitment of epigenetic modifiers to alter local chromatin accessibility and histone marks (Puffer et al., 2020).