mutation, but most are silenced by DNA methylation. Others are regulated promoters. Selection may favor less energetic transcriptional binding. Variations in promoters or transcription factors cause some diseases. Misunderstandings can result from using canonical sequence to describe a promoter. Overview For transcription to take place, the enzyme that synthesizes RNA, known as RNA polymerase, must attach to the DNA near a gene. Promoters contain specific DNA sequences such as response elements that provide a secure initial binding site for RNA polymerase and for proteins called transcription factors that recruit RNA polymerase. These transcription factors have specific activator or repressor sequences of corresponding nucleotides that attach to specific promoters and regulate gene expression. In bacteria The promoter is recognized by RNA polymerase and an associated sigma factor, which in turn are often brought to the promoter DNA by an activator protein's binding to its own DNA binding site nearby. In eukaryotes The process is more complicated, and at least seven different factors are necessary for the binding of an RNA polymerase II to the promoter. Promoters represent critical elements that can work in concert with other regulatory regions (enhancers, silencers, boundary elements/insulators) to direct the level of transcription of a given gene. A promoter is induced in response to changes in abundance or conformation of regulatory proteins in a cell, which enable activating transcription factors to recruit RNA polymerase. Identification of relative location As promoters are typically immediately adjacent to the gene in question, positions in the promoter are designated relative to the transcriptional start site, where transcription of DNA begins for a particular gene (i.e., positions upstream are negative numbers counting back from -1, for example -100 is a position 100 base pairs upstream). Relative location in the cell nucleus In the cell nucleus, it seems that promoters are distributed preferentially at the edge of the chromosomal territories, likely for the co-expression of genes on different chromosomes. Furthermore, in humans, promoters show certain structural features characteristic for each chromosome. Elements Bacterial In bacteria, the promoter contains two short sequence elements approximately 10 (Pribnow Box) and 35 nucleotides upstream from the transcription start site. The sequence at -10 (the -10 element) has the consensus sequence TATAAT. The sequence at -35 (the -35 element) has the consensus sequence TTGACA. The above consensus sequences, while conserved on average, are not found intact in most promoters. On average, only 3 to 4 of the