In eukaryotic cells, transcription factors are proteins that can bind to DNA and regulate the expression of genes. In order to initiate transcription, each RNA polymerase requires several different proteins, called general transcription factors, to bind to promoter regions. For example, the first and largest of these proteins, called TFIID, will bind to the TATA Box region found in most promoters. Along with other proteins, they recruit the polymerase to the promoter region and form the pre-initiation complex.

Specific transcription factors, on the other hand, can bind to distal regulatory regions called enhancer sites, away from the transcription start site, sometimes thousands of base pairs upstream or downstream of a gene, and induce higher rates of transcription. In a process called looping, the DNA strand will bend in a way that allows transcription factors bound to enhancer sites to establish protein-protein interactions with mediator proteins and the pre-initiation complex. Specific transcription factors that bind to enhancer sites to promote transcription are known as activators, while those that block or reduce transcription are called repressors. The presence of specific transcription factors and distal regulatory elements allows for differential gene expression, such as the turning on or off of different genes during early development to determine whether the cell will become a skin cell or a neuron, as well as the coordinated transcription of related functional genes.

Over 1,500 different transcription factors have been identified in humans that regulate a wide range of critical genes, from the determination of cell types early in development to the cellular response to different environmental conditions.