Sp1 modification of human endothelial nitric oxide synthase promoter increases the hypoxia-stimulated activity

Yang, Yunhua; Liu, Song; Fan, Zhenhua; Li, Zhuo; Liu, Jing; Xing, Feiyue

doi:10.1016/j.mvr.2014.03.004

Cited by 5 publications

(4 citation statements)

References 49 publications

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“…A previous study showed that Sp1 regulates eNOS expression by binding to the eNOS promoter G/C box region (−109 to −95 in the human eNOS promoter) [ 21 ]. From this study, we hypothesized that ZEN increases the binding of Sp1 to its target DNA site, i.e., G/C-rich regions within the human eNOS promoter (−135 to +22), consequently decreasing the mRNA transcriptional activity of eNOS.…”

Section: Resultsmentioning

confidence: 99%

Zearalenone-Induced Interaction between PXR and Sp1 Increases Binding of Sp1 to a Promoter Site of the eNOS, Decreasing Its Transcription and NO Production in BAECs

Lee

Park

et al. 2020

Toxins

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Zearalenone (ZEN) is a non-steroidal mycotoxin that has various toxicological impacts on mammalian health. Here, we found that ZEN significantly affected the production of nitric oxide (NO) and the expression of endothelial NO synthase (eNOS) of bovine aortic endothelial cells (BAECs). A promoter analysis using 5′-serially deleted human eNOS promoter revealed that the proximal region (−135 to +22) was responsible for ZEN-mediated reduction of the human eNOS promoter activity. This effect was reversed by mutation of two specificity protein 1 (Sp1) binding elements in the human eNOS promoter. A chromatin immunoprecipitation assay revealed that ZEN increased Sp1 binding to the bovine eNOS promoter region (−113 to −12), which is homologous to −135 to +22 of the human eNOS promoter region. We also found that ZEN promoted the binding of the pregnane X receptor (PXR) to Sp1 of the bovine eNOS, consequently decreasing eNOS expression. This reduction of eNOS could have contributed to the decreased acetylcholine-induced vessel relaxation upon ZEN treatment in our ex vivo study using mouse aortas. In conclusion, our data demonstrate that ZEN decreases eNOS expression by enhancing the binding of PXR-Sp1 to the eNOS promoter, thereby decreasing NO production and potentially causing vessel dysfunction.

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Section: Resultsmentioning

confidence: 99%

Zearalenone-Induced Interaction between PXR and Sp1 Increases Binding of Sp1 to a Promoter Site of the eNOS, Decreasing Its Transcription and NO Production in BAECs

Lee

Park

et al. 2020

Toxins

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“…The functional consequence of non-CG methylation is currently unclear but its presence can directly inhibit the binding of specificity protein 1 (Sp1) 29 . Sp1 contributes to the maintenance of methylation-free CpG islands 30 and can increase promoter activity 31 , as well as regulating a variety of cellular processes including tissue-specific transcriptional activity 32 , cell differentiation and chromatin remodelling 33 . Experiments carried out by Clark et al .…”

Section: Discussionmentioning

confidence: 99%

Non-CG DNA methylation is a biomarker for assessing endodermal differentiation capacity in pluripotent stem cells

et al. 2016

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Non-CG methylation is an unexplored epigenetic hallmark of pluripotent stem cells. Here we report that a reduction in non-CG methylation is associated with impaired differentiation capacity into endodermal lineages. Genome-wide analysis of 2,670 non-CG sites in a discovery cohort of 25 phenotyped human induced pluripotent stem cell (hiPSC) lines revealed unidirectional loss (Δβ=13%, P<7.4 × 10−4) of non-CG methylation that correctly identifies endodermal differentiation capacity in 23 out of 25 (92%) hiPSC lines. Translation into a simplified assay of only nine non-CG sites maintains predictive power in the discovery cohort (Δβ=23%, P<9.1 × 10−6) and correctly identifies endodermal differentiation capacity in nine out of ten pluripotent stem cell lines in an independent replication cohort consisting of hiPSCs reprogrammed from different cell types and different delivery systems, as well as human embryonic stem cell (hESC) lines. This finding infers non-CG methylation at these sites as a biomarker when assessing endodermal differentiation capacity as a readout.

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“…Copy@ Ally A, Nauli S in humans is encoded by the SP1 gene and is critically involved in various cellular processes that may include cell differentiation, cell proliferation, apoptosis, immune responses, chromatin remodeling, and even DNA damage [57]. There are also post- the nucleus to the cytoplasm [61].…”

Section: Am J Biomed Sci and Resmentioning

confidence: 99%

Endothelial Nitric Oxide Synthase (eNOS) and the Cardiovascular System: in Physiology and in Disease States

Nauli

2022

AJBSR

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erectile dysfunction [7]; the role of the eNOS enzyme, including its modulation, regulation, and relevance within the cardiovascular system (CVS) in both normal physiological state and in several important cardiovascular diseases is elaborated. In addition, because the amount of NO generated by the vascular endothelial cells plays critical roles in the regulation and maintenance of the vascular tone, migration, production, proliferation, and maturation of cells, leukocyte adhesion, and platelet aggregation, it can be implied that eNOS is indeed an essential molecule for a properly functioning and healthy CVS, thus emphasizing the protective action of eNOS on the CVS.

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Sp1 modification of human endothelial nitric oxide synthase promoter increases the hypoxia-stimulated activity

Cited by 5 publications

References 49 publications

Zearalenone-Induced Interaction between PXR and Sp1 Increases Binding of Sp1 to a Promoter Site of the eNOS, Decreasing Its Transcription and NO Production in BAECs

Zearalenone-Induced Interaction between PXR and Sp1 Increases Binding of Sp1 to a Promoter Site of the eNOS, Decreasing Its Transcription and NO Production in BAECs

Non-CG DNA methylation is a biomarker for assessing endodermal differentiation capacity in pluripotent stem cells

Endothelial Nitric Oxide Synthase (eNOS) and the Cardiovascular System: in Physiology and in Disease States

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