General transcription factors (GTFs), also known as basal transcriptional factors, are a class of protein transcription factors that bind to specific sites (promoter) on DNA to activate transcription of genetic information from DNA to messenger RNA. GTFs, RNA polymerase, and the mediator (a multi-protein complex) constitute the basic transcriptional apparatus that first bind to the promoter, then start transcription. GTFs are also intimately involved in the process of gene regulation, and most are required for life. A transcription factor is a protein that binds to specific DNA sequences (enhancer or promoter), either alone or with other proteins in a complex, to control the rate of transcription of genetic information from DNA to messenger RNA by promoting (serving as an activator) or blocking (serving as a repressor) the recruitment of RNA polymerase. As a class of protein, general transcription factors bind to promoters along the DNA sequence or form a large transcription preinitiation complex to activate transcription. General transcription factors are necessary for transcription to occur. Types In bacteria, transcription initiation requires an RNA polymerase and a single GTF: sigma factor. In archaea and eukaryotes, transcription initiation requires an RNA polymerase and a set of multiple GTFs to form a transcription preinitiation complex. The Transcription initiation by eukaryotic RNA polymerase II involves the following GTFs: TFIIA - Stabilizes the interaction between the TATA box and TFIID/TATA binding protein (TBP) TFIIB - recognizes the BRE element in promoters TFIID – binds to TBP and recognizes TBP associated factors (TAFs), also adds promoter selectivity TFIIE - attracts and regulates TFIIH TFIIF - Stabilizes RNA polymerase interaction with TBP and TFIIB; helps attract TFIIE and TFIIH TFIIH - Unwinds DNA at the transcription start point, phosphorylates Ser5 of the RNA polymerase CCTD, releases RNA polymerase from the promoter Function and mechanism In bacteria A sigma factor is a protein needed only for initiation of RNA synthesis in bacteria. Sigma factors provide promoter recognition specificity to the RNA polymerase (RNAP) and contribute to DNA strand separation, then dissociating from the RNA polymerase core enzyme following transcription initiation. The RNA polymerase core associates with the sigma factor to form RNA polymerase holoenzyme. Sigma factor reduces the affinity of RNA polymerase for nonspecific DNA while increasing specificity for promoters, allowing transcription to initiate at correct sites. The core enzyme of RNA polymerase has five subunits (protein subunits) (~400 kDa). Because of the RNA polymerase association with sigma