14.3: Transcription Factors

Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of specific tissues or body parts without affecting the entire organism.

An additional layer of complexity is added by transcription factors in eukaryotes exerting combinatorial control. That means input provided by several transcription factors synchronously regulates the expression of a single gene. The combination of several transcriptional activators and repressors enables a gene to be differentially regulated and adapt to a variety of environmental changes without the need for additional genes.

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.