GTF2B Human
Description
Product Specs
Product Science Overview
TFIIB is a single polypeptide consisting of 316 amino acids with a molecular weight of approximately 33 kDa . It is composed of four functional regions:
- C-terminal core domain
- B linker
- B reader
- Amino terminal zinc ribbon
These regions facilitate interactions with various components of the transcription machinery, including the TATA-binding protein (TBP) and RNA polymerase II . TFIIB binds and stabilizes the DNA-TBP complex, recruits RNA polymerase II, and other transcription factors to form the PIC .
The mechanism of TFIIB action in transcription initiation involves several steps :
- Recruitment of RNA polymerase II to DNA through the TFIIB B core and B ribbon.
- Unwinding of DNA by RNA polymerase II, aided by the TFIIB B linker and B reader.
- Selection of a transcription start site by RNA polymerase II, aided by the TFIIB B reader.
- Formation of the first phosphodiester bond by RNA polymerase II.
- Production of short abortive transcripts due to clashes between nascent RNA and the TFIIB B reader loop.
- Extension of nascent RNA to 12-13 nucleotides, leading to the ejection of TFIIB due to further clashes with TFIIB.
TFIIB is localized to the nucleus and provides a platform for PIC formation by binding and stabilizing the DNA-TBP complex and recruiting RNA polymerase II and other transcription factors . It is encoded by the TFIIB gene and is homologous to archaeal transcription factor B and analogous to bacterial sigma factors .
Research has shown that TFIIB and cyclin-dependent kinase 9 (Cdk9) are upregulated during cardiac hypertrophy . TFIIB is constitutively bound to all paused, housekeeping promoters, whereas de novo recruitment of TFIIB and polymerase II is required for specialized genes induced during hypertrophy . This dichotomy has been exploited to acutely inhibit the induction of specialized genes, which encompass cardiomyopathy, immune reaction, and extracellular matrix genes, using locked nucleic acid-modified antisense TFIIB oligonucleotide treatment .
By targeting TFIIB, researchers were able to selectively inhibit the induction of specialized genes and ameliorate pressure overload hypertrophy . This demonstrates the feasibility of acutely and reversibly targeting cardiac mRNA for therapeutic purposes using locked nucleic acid-modified antisense oligonucleotides .
