Oct3/4 Signaling Pathway

1. Oct3/4 Signaling Pathway OCT3/4 (encoded by Pou5f1, also known as OCT3, OCT4) was first identified in mice as an ESC-specific and germline-specific transcription factor. In humans, OCT4 is the product of the OTF3 gene, and has been reported to have three isoforms, OCT4A, OCT4B and OCT4B1. Among these isoforms, only OCT4A – which shares 87% amino acid sequence identity with mouse OCT4 – has been demonstrated to maintain the pluripotency of stem cells; it is referred to as OCT4 in the vast majority of reports. The Oct4 gene is driven by a TATA-less promoter, a proximal enhancer (PE) and a distal enhancer (DE). Comparative analysis of Oct4 regulatory elements in different species identified four conservative regions (CRs): CR1 (in proximal promoter), CR2 and CR3 (PE), as well as CR4 (DE). The DE/CR4 is essential for regulating Oct4 expression in morula, inner cell mass of blastocysts and primordial germ cells; while the PE/CR2 activates Oct4 in the epiblast stage. Several positive and negative regulators bind to the Oct4 gene to regulate its expression. LRH-1 binds to the PE and activates Oct4 in undifferentiated ES cells through an uncharacterized mechanism. Other positive regulators include SF1 (Steroidogenic Factor-1) and RXR-Beta (Retinoid X Receptor-Beta). As a separate mechanism, retinoic acid induces GCNF (early period) and ARP-1/COUP-TFII and EAR-3/COUP-TFII (late period) contribute to the suppression of the Oct4 gene. Wwp2 (WW domain containing E3 Ubiquitin Protein ligase-2) can directly bind to OCT4 through WW domains. It promotes ubiquitination of OCT4, leading to the degradation of OCT4. https://www.creative-diagnostics.com/oct3-4-signaling-pathway.htm