Any of a group of proteins that work synergistically to regulate gene activity by increasing or decreasing the binding of RNA polymerases to the DNA molecule during the process of transcription. This is achieved by the ability of the transcription factors to bind to the DNA molecule (see DNA-binding proteins). Transcription factors contain finger domains, which are often in repeated sequences called multifinger loops. In eukaryotes general transcription factors are active in the transcription of all genes. First, several bind to the promoter site near to the transcription start site and ensure the correct positioning of RNA polymerase II with respect to the coding region of the gene. Binding of additional transcription factors and other proteins forms the initiation complex, and enables RNA polymerase II to unwind the DNA double helix and begin RNA synthesis. However, efficient transcription of many genes requires regulatory transcription factors, which determine whether the gene is switched ‘on’ or ‘off’ by binding to regulatory sites called control elements. Proximal control elements are located near to the promoter, whereas distal control elements, grouped together to form enhancers, may be located many thousands of base pairs from the coding region. The binding of activators or repressors to these control elements is crucial to regulating transcription. Another mechanism involves the recruitment of chromatin-modifying proteins by activators or repressors. These add or remove acetyl groups on the histone proteins of chromatin near the promoter, thus promoting or silencing transcription. These mechanisms in eukaryotes are crucial in ensuring that genes are expressed in a tissue-dependent manner and, during development, that genes are expressed at the appropriate time and place within the embryo. Hundreds of transcription factors may be involved in controlling just one gene. Many cellular signal transduction pathways, triggered by the binding of a substance to its receptor on the cell surface, ultimately lead to the phosphorylation and activation of transcription factors in the nucleus, and hence alterations in gene expression. See also operon; sigma factor.