Transcriptional co-activator and basal transcription machinery (VP64-recruited) (VP64-recruited machinery)

VP64 is a potent synthetic transcriptional activator composed of four tandem repeats of the Herpes Simplex Virus VP16 minimal activation domain. It functions by recruiting a suite of endogenous proteins, known as generic transcriptional co-activators and the basal transcription machinery, to a specific genomic locus [Perez-Pinera et al., 2013, Nature Methods]. Key components recruited by this domain include the Mediator complex, histone acetyltransferases like p300/CBP, and general transcription factors such as TFIID and TFIIB [Hall and Struhl, 2002, Nature]. This recruitment facilitates the assembly of the pre-initiation complex and the subsequent recruitment of RNA polymerase II, leading to the robust upregulation of target gene expression [Maeder et al., 2013, Nature Methods]. While not a single therapeutic target itself, this machinery serves as the effector arm for various gene modulation technologies, including CRISPR activation (CRISPRa), Zinc Finger activators, and TALE activators. These systems are being explored for treating haploinsufficiency disorders, inducing cellular reprogramming, and compensating for lost gene function in various diseases [Konermann et al., 2015, Nature]. The use of VP64-mediated recruitment allows for precise control over endogenous gene expression without the need for exogenous cDNA delivery.

Other names

VP64-associated transcriptional complexVP16-derived activation complexBasal transcription apparatusTranscriptional co-activator complex

Recruitment of the basal transcription machinery and chromatin-modifying enzymes to a target promoter to initiate mRNA synthesis.