scholarly journals Reprogramming progressive cells display low CAG promoter activity

Stem Cells ◽  
2020 ◽  
Vol 39 (1) ◽  
pp. 43-54
Author(s):  
Xiao Hu ◽  
Qiao Wu ◽  
Jian Zhang ◽  
Jonghun Kim ◽  
Xinyue Chen ◽  
...  
Keyword(s):  
Promoter Activity ◽  
Cag Promoter

scholarly journals Reprogramming progressive cells display low CAG promoter activity

2020 ◽  
Author(s):  
Xiao Hu ◽  
Qiao Wu ◽  
Jian Zhang ◽  
Xinyue Chen ◽  
Amaleah Hartman ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Promoter Activity ◽  
Human Fibroblasts ◽  
Small Cell ◽  
Synthetic Promoter ◽  
Small Cell Size ◽  
Wide Variability ◽  
Yamanaka Factors ◽  
Cag Promoter ◽  
Low Activity

AbstractThere is wide variability in the propensity of somatic cells to reprogram into pluripotency in response to the Yamanaka factors. How to segregate these variability to enrich for cells of specific traits that reprogram efficiently remains challenging. Here we report that the variability in reprogramming propensity is associated with the activity of the MKL1/SRF transcription factor and concurs with small cell size as well as rapid cell cycle. Reprogramming progressive cells can be prospectively identified by their low activity of a widely used synthetic promoter, CAG. CAGlow cells arise and expand during cell cycle acceleration in the early reprogramming culture of both mouse and human fibroblasts. Our work illustrate a molecular scenario underlying the distinct reprogramming propensities and demonstrate a convenient practical approach for their enrichment.

Developmental regulation of the composite CAG promoter activity in the murine T lymphocyte cell lineage

genesis ◽  
2009 ◽  
pp. NA-NA ◽  
Author(s):  
Delphine Baup ◽  
Muriel Moser ◽  
Stéphane Schurmans ◽  
Oberdan Leo
Keyword(s):  
T Lymphocyte ◽  
Promoter Activity ◽  
Developmental Regulation ◽  
Cell Lineage ◽  
Lymphocyte Cell ◽  
Cag Promoter

Novel Mechanisms of Tumor Promoter Activity by Estrogenic Xenobiotics

2000 ◽  
Author(s):  
Robert M. Bigsby
Keyword(s):  
Promoter Activity ◽  
Tumor Promoter

Growth Retardation of Poorly Transfectable Tumor by Multiple Injections of Plasmids Encoding PE40 Based Targeted Toxin Complexed with Polyethylenimine

2020 ◽  
Vol 20 (4) ◽  
pp. 289-296
Author(s):  
Yuriy Khodarovich ◽  
Darya Rakhmaninova ◽  
German Kagarlitskiy ◽  
Anastasia Baryshnikova ◽  
Sergey Deyev
Keyword(s):  
Growth Retardation ◽  
Bystander Effect ◽  
Dna Encoding ◽  
Complex Preparation ◽  
Human Telomerase ◽  
Linear Polyethylenimine ◽  
Cag Promoter ◽  
Targeted Toxin

Background:: One of the approaches to cancer gene therapy relies on tumor transfection with DNA encoding toxins under the control of tumor-specific promoters. Methods:: Here, we used DNA plasmids encoding very potent anti-ERBB2 targeted toxin, driven by the human telomerase promoter or by the ubiquitous CAG promoter (pTERT-ETA and pCAG-ETA) and linear polyethylenimine to target cancer cells. Results:: We showed that the selectivity of cancer cell killing by the pTERT-ETA plasmid is highly dependent upon the method of preparation of DNA-polyethylenimine complexes. After adjustment of complex preparation protocol, cell lines with high activity of telomerase promoter can be selectively killed by transfection with the pTERT-ETA plasmid. We also showed that cells transfected with pTERT-ETA and pCAG-ETA plasmids do not exert any detectable bystander effect in vitro. Conclusion:: Despite this, three intratumoral injections of a plasmid-polyethylenimine complex resulted in substantial growth retardation of a poorly transfectable D2F2/E2 tumor in mice. There were no significant differences in anti-tumor properties between DNA constructs with telomerase or CAG promoters in vivo.

UBE2L6 is Involved in Cisplatin Resistance by Regulating the Transcription of ABCB6

2020 ◽  
Vol 20 (12) ◽  
pp. 1487-1496 ◽  
Author(s):  
Midori Murakami ◽  
Hiroto Izumi ◽  
Tomoko Kurita ◽  
Chiho Koi ◽  
Yasuo Morimoto ◽  
...  
Keyword(s):  
Gene Expression ◽  
Promoter Activity ◽  
Anticancer Agent ◽  
Cisplatin Resistance ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Molecular Target ◽  
Transcriptional Level ◽  
And Control ◽  
Resistant Cells

Background: Cisplatin is an important anticancer agent in cancer chemotherapy, but when resistant cells appear, treatment becomes difficult, and the prognosis is poor. Objective: In this study, we investigated the gene expression profile in cisplatin sensitive and resistant cells, and identified the genes involved in cisplatin resistance. Methods: Comparison of gene expression profiles revealed that UBE2L6 mRNA is highly expressed in resistant cells. To elucidate whether UBE2L6 is involved in the acquisition of cisplatin resistance, UBE2L6- overexpressing cells established from cisplatin-sensitive cells and UBE2L6-silenced cells developed from cisplatin- resistant cells were generated, and the sensitivity of cisplatin was examined. Results: The sensitivity of the UBE2L6-overexpressing cells did not change compared with the control cells, but the UBE2L6-silenced cells were sensitized to cisplatin. To elucidate the mechanism of UBE2L6 in cisplatin resistance, we compared the gene expression profiles of UBE2L6-silenced cells and control cells and found that the level of ABCB6 mRNA involved in cisplatin resistance was decreased. Moreover, ABCB6 promoter activity was partially suppressed in UBE2L6-silenced cells. Conclusion: These results suggest that cisplatin-resistant cells have upregulated UBE2L6 expression and contribute to cisplatin resistance by regulating ABCB6 expression at the transcriptional level. UBE2L6 might be a molecular target that overcomes cisplatin resistance.

scholarly journals The Glucocorticoid Receptor (GR) Stimulates Herpes Simplex Virus 1 Productive Infection, in Part Because the Infected Cell Protein 0 (ICP0) Promoter Is Cooperatively Transactivated by the GR and Krüppel-Like Transcription Factor 15

2019 ◽  
Vol 93 (6) ◽  
Author(s):  
Jeffery B. Ostler ◽  
Kelly S. Harrison ◽  
Kayla Schroeder ◽  
Prasanth Thunuguntla ◽  
Clinton Jones
Keyword(s):  
Transcription Factor ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Infected Cell ◽  
Promoter Activity ◽  
Productive Infection ◽  
Cell Protein ◽  
Herpes Simplex Virus 1 ◽  
Infected Cell Protein ◽  
Infected Cell Protein 0

ABSTRACTFollowing acute infection, herpes simplex virus 1 (HSV-1) establishes lifelong latency in neurons. Physical, emotional, and chemical stresses are linked to increasing the incidence of reactivation from latency, but the mechanism of action is not well understood. In general, stress increases corticosteroid levels, leading to activation of the glucocorticoid receptor (GR), a pioneer transcription factor. Consequently, we hypothesized that stress-mediated activation of the GR can stimulate productive infection and viral gene expression. New studies demonstrated that the GR-specific antagonist (CORT-108297) significantly reduced HSV-1 productive infection in mouse neuroblastoma cells (Neuro-2A). Additional studies demonstrated that the activated GR and Krüppel-like transcription factor 15 (KLF15) cooperatively transactivated the infected cell protein 0 (ICP0) promoter, a crucial viral regulatory protein. Interestingly, the synthetic corticosteroid dexamethasone and GR or KLF15 alone had little effect on ICP0 promoter activity in transfected Neuro-2A or Vero cells. Chromatin immunoprecipitation (ChIP) studies revealed that the GR and KLF15 occupied ICP0 promoter sequences important for transactivation at 2 and 4 h after infection; however, binding was not readily detected at 6 h after infection. Similar results were obtained for cells transfected with the full-length ICP0 promoter. ICP0 promoter sequences lack a consensus “whole” GR response element (GRE) but contain putative half-GREs that were important for dexamethasone induced promoter activity. The activated GR stimulates expression of, and interacts with, KLF15; consequently, these data suggest KLF15 and the GR form a feed-forward loop that activates viral gene expression and productive infection following stressful stimuli.IMPORTANCEThe ability of herpes simplex virus 1 (HSV-1) to periodically reactivate from latency results in virus transmission and recurrent disease. The incidence of reactivation from latency is increased by chronic or acute stress. Stress increases the levels of corticosteroids, which bind and activate the glucocorticoid receptor (GR). Since GR activation is an immediate early response to stress, we tested whether the GR influences productive infection and the promoter that drives infected cell protein 0 (ICP0) expression. Pretreatment of cells with a GR-specific antagonist (CORT-108297) significantly reduced virus replication. Although the GR had little effect on ICP0 promoter activity alone, the Krüppel-like transcription factor 15 (KLF15) cooperated with the GR to stimulate promoter activity in transfected cells. In transfected or infected cells, the GR and KLF15 occupied ICP0 sequences important for transactivation. Collectively, these studies provide insight into how stress can directly stimulate productive infection and viral gene expression.

Sign in / Sign up

Export Citation Format

Share Document