CorePromoters

CorePromoters are the minimal DNA sequences surrounding a gene's transcription start site that are sufficient to initiate transcription when bound by the basal transcription machinery. Positioned typically within roughly -40 to +40 nucleotides relative to the transcription start site, they recruit RNA polymerase II and general transcription factors necessary for the formation of the transcriptional pre-initiation complex.

Core promoter elements vary; common motifs include the TATA box, initiator (Inr), downstream promoter element (DPE), and motif ten element (MTE). The TATA box is found in a subset of promoters and helps specify precise start sites, whereas Inr and DPE can function without a TATA box. Some promoters have broad initiation patterns with multiple weak motifs.

Promoter architecture influences transcriptional strength and responsiveness; core promoters interact with proximal regulatory elements, enhancers, and chromatin context to determine transcription levels. Differences in promoter types, such as sharp (narrow, focused TSS) versus broad (distributed TSS), reflect distinct regulatory programs.

Endogenous mapping methods such as CAGE, RAMPAGE, and GRO-seq are used to map transcription start sites and infer core promoter locations. Comparative genomics reveals conservation of motifs across species, while functional assays using reporter constructs test promoter activity.

Clinical relevance: Variation in core promoter sequences can alter gene expression and contribute to disease phenotypes; core promoter mutations are studied in human genetics.