In eukaryotic cells, the TATA box on the promoter combines with the transcription factor TFIID to form a stable complex, and then other transcription factors (TFIIA, TFIIB, TFIIF, TFIIE, TFIIH, etc.) and RNA polymerase are combined with DNA to form a certain sequence. Transcription initiation complex. The transcription initiation complex is the "molecular machine" that initiates transcription. When TBP (TATA binding protein) -containing transcription factors interact with DNA, other factors also combine to form a complex, which is then polymerized with RNA. Enzyme binding eventually forms a transcription initiation complex.

TAF1 family

The transcription initiation factor TFIID subunit 1, also known as the transcription initiation factor TFIID 250 kDa subunit (TAFII-250) or TBP-related factor 250 kDa (p250), is a protein encoded by the TAF1 gene in humans.

Figure 1. Protein structure of TAF1.

Functions

Initiation of transcription by RNA polymerase II requires the activity of more than 70 polypeptides. The protein that coordinates these activities is the basic transcription factor TFIID, which binds to the core promoter to correctly locate the polymerase, acts as a scaffold to assemble the rest of the transcription complex, and acts as a channel for regulatory signals. TFIID consists of a TATA-binding protein (TBP) and a group of evolutionarily conserved proteins called TBP-related factors or TAF. TAF may participate in basal transcription, act as a co-activator, play a role in promoter recognition or modify the general transcription factor (GTF) to facilitate complex assembly and transcription initiation. This gene encodes the largest subunit of TFIID. This subunit binds to a core promoter sequence containing a transcription start site. It also binds activators and other transcriptional regulators, and these interactions affect the rate of transcription initiation. This subunit contains two independent protein kinase domains at the N- and C-termini, but also has acetyltransferase activity and can act as a ubiquitin activating/conjugating enzyme. Two transcripts encoding different isoforms have been identified for this gene. Histones are often acetylated to turn on DNA for transcription. TAF1 contains two bromodomains, each of which can bind one of the two acetyllysine residues at positions 5 and 12 of the H4 tail to stabilize the TBP-TATA box complex.

Clinical significance

Identified TAF1 mutations can lead to phenotypes with severe intellectual disability (ID), typical hip creases, and unique facial features, including a broad nose, drooping cheeks, tilted blepharoptosis, and prominent orbital spine The staring eyes, the relative vitreous hypertrophy, the thin upper lip, the arch of the upper jaw, the protruding ears, the spiral thickening and the tip of the chin. This is a non-synonymous change in TAF1 that results in a change in threonine (polarity) at the 1337th amino acid residue in the isoleucine (hydrophobic) protein. Although no more clinical details have been reported, TAF1 has also reported two other mutations in two families with intellectual disability.

TAF2

The transcription initiation factor TFIID subunit 2 is a protein encoded by the TAF2 gene in humans. The transcription initiation of RNA polymerase II requires the activity of more than 70 polypeptides. The protein that coordinates these activities is the transcription factor IID (TFIID), which binds to the core promoter to correctly position the polymerase, acts as a scaffold to assemble the rest of the transcription complex, and acts as a channel for regulatory signals. TFIID consists of TATA binding protein (TBP) and a group of evolutionarily conserved proteins called TBP-related factors or TAF. TAF may participate in basal transcription, act as a co-activator, play a role in promoter recognition or modify the general transcription factor (GTF) to facilitate complex assembly and transcription initiation. This gene encodes one of the larger TFIID subunits associated with the stability of the TFIID complex. It facilitates the transcription initiation site and its downstream interactions, which help determine the response of transcription complexes to activators.

References:

1. Martinez E; et al. Novel cofactors and TFIIA mediate functional core promoter selectivity by the human TAFII150-containing TFIID complex .1998.