Transcription factor

Transcription factors are a family of proteins that bind to DNA and thereby regulate the transcription of genes. Transcription factors themselves are coded for by genes, and in the human genome 10% of genes code for transcription factors making them the largest family of human proteins. They are very well conserved in nature, being found in every living organism and viruses alike.

Transcription factors are distinct from other proteins involved in gene transcription because they have a DNA-binding domain. Other proteins, such as the enzymes that catalyse histone acetylation, may influence the rate of transcription, but they do not themselves bind to DNA and thus are not considered transcription factors.

Transcription factors bind at a locus adjacent to the gene whose transcription is to be regulated at sequences called response elements, found usually, but not always, in the promoter region. The factors may either enhance the rate of transcription (in the case of activators) or reduce it (in the case of repressors). Transcription factors often act by either enhancing or reducing the binding affinity of RNA polymerase for the gene, thereby enhancing or reducing the ability of RNA polymerase to transcribe that gene. Alternatively, the transcription factor may recruit a histone (de)acetylase to alter the interaction of histone proteins and DNA and determine the rate of transcription by DNA accessibility. Regardless of the mechanism employed, any increase in gene transcription is called upregulation, while any decrease is called downregulation.

Transcription factors often have another domain called a signal-sensing domain. This region of the protein is capable of binding molecules, such as nuclear hormones like testosterone and oestrogen, which either activate or deactivate the transcription factor. This is how hormones influence gene expression and, for instance, muscle growth genes are only active in the presence of sufficient testosterone. Transcription factors may also be activated by phosphorylation of certain amino acid residues, or dimerization with either other transcription factors or other co-regulatory proteins (such as co-activators or co-repressors, which are not themselves transcription factors due to the absence of a DNA-binding domain). In fact, co-regulatory proteins bind to yet another domain on the transcription factor, called a trans-activating domain.

A complex of transcription factors is involved in forming the pre-initiation complex during eukaryotic transcriptional initiation. These factors bind promoter consensus sequences such as the TATA box in their DNA-binding domain, as well as either other transcription factors or RNA polymerase itself in their trans-activating domain.

Because transcription factors are themselves synthesised from genes via protein biosynthesis, they may act on their own genes to downregulate further transcription of themselves. In this way, transcription factors are capable of a very efficient negative feedback loop to prevent the energy costs in producing excessive amounts of themselves.