Functional characterization of the Sox2, c‐Myc, and Oct4 promoters

Abstract

To better understand the mechanisms in transcriptional regulation, we analyzed the promoters of the reprogramming key genes Sox2, c‐Myc, and Oct4. Here, we cloned different 5′ deletions of the goat Sox2, c‐Myc, and Oct4 promoters, and evaluated their functions by green fluorescent protein reporter system and dual‐luciferase reporter system. Site‐directed mugagenesis and epigenetic modifiers were used to explore the influence of transcription binding sites and epigenetic status on the promoters. The results suggested that the basal promoters were located in the − 109 to 49, − 147 to 1, and − 96 to 30 bp regions of the Sox2, c‐Myc, and Oct4 promoters. The transcription factors that identified to influence the Sox2, c‐Myc, and Oct4 promoter activities were Elf‐1 and activating protein 2 (AP‐2), C/EBP and Sp1, and Mzf1 and Sp1, respectively. The epigenetic alternation of the Sox2, c‐Myc, and Oct4 promoters by 5‐aza‐2′‐deoxycytidine or/and trichostatin A significantly increased the promoter activities. In conclusion, the result determined the core promoter areas of the Sox2, c‐Myc, and Oct4 genes, and identified the transcription factors that influence their promoter activities. We also verified that the Sox2, c‐Myc, and Oct4 promoters were hypermethylated and hypoacetylated.

Tspan8-Tumor Extracellular Vesicle-Induced Endothelial Cell and Fibroblast Remodeling Relies on the Target Cell-Selective Response

“…Tf NFκB p65 1 expression remained unaltered, whereas predominantly AS-Tspan8-TEX promoted Jun 1 , FOS 1 , HIF1α 1 , and SMAD4 1 upregulation. Foxo3 1 as well as eLF1 1 , a component of the RNA polymerase II elongation complex regulating c-Myc 1 , Sox2 1 , and Oct4 1 [63,64] were strongly elevated after AS-Tspan8-TEX treatment ( Figure 4E). Some RTK, most strongly NTRK1 1 , NTRK2 1 , TYRO3 1 , and VEGFR2 1 and less pronounced ALK 1 , ErbB3 1 , and MET 1 became only upregulated by AS-Tspan8-TEX.…”

“…Increased NOX1 and NOX4 expression could predominantly cope with ROS during premetastatic niche preparation in advance of angiogenesis induction [61,62]. Of particular interest also appeared the upregulated expression of eLF1, a component of the RNA polymerase II elongation complex that was identified as one of the Tf influencing the promoter activity of c-Myc, Sox2, and Oct4 [63,64]. For some additional upregulated proteins the mode of action being not yet defined or controversially discussed, we proceeded searching for overrepresented edges.…”

IL-1RA promotes oral squamous cell carcinoma malignancy through mitochondrial metabolism-mediated EGFR/JNK/SOX2 pathway

“…Also, whether IL-1RA-activated EGFR transduces signals via its receptor tyrosine kinase activity or via translocation to intracellular organelles remains to be determined. The genetic control of SOX2 expression induced by IL-1RA in OSCC cells also requires further investigation, such as the potential for transcriptional regulation by c-Jun, which can bind to the promoter region of SOX2 [ 75 , 76 ]. Furthermore, apart from the effect of metformin on in vivo tumor growth examined in this study, the therapeutic potential of metformin on metastasis in a pre-clinical in vivo model merits further investigation.…”

Understanding the Role of the Transcription Factor Sp1 in Ovarian Cancer: from Theory to Practice

“…Sp1 transcription factors, were recognized as central regulators of the switch genes, displaying their potential role in cellular reprogramming [102]. Sp1 is one of the most important transcription factors that are associated with the major reprogramming factors Sox2, c-Myc, and Oct4, that are used for IPSC induction (Figure 4) [103]. Similarly, when goats IPSCs were generated, it was observed that the core genes previously mentioned had Sp1 binding sites in their core promoter.…”