A G-quadruplex nanoswitch in the SGK1 promoter regulates isoform expression by K+/Na+ balance and resveratrol binding. Chen, M., Chen, Q., Li, Y., Yang, Z., Taylor, E. W., & Zhao, L. Biochimica et Biophysica Acta (BBA) - General Subjects, 1865(2):129778, February, 2021. tex.ids= chenGquadruplexNanoswitchSGK12021
A G-quadruplex nanoswitch in the SGK1 promoter regulates isoform expression by K+/Na+ balance and resveratrol binding [link]Paper  doi  abstract   bibtex   
Background High sodium intake can up-regulate the level of renal serum- and glucocorticoid-inducible kinase-1 (SGK1), which plays a pivotal role in controlling blood pressure via activation of the epithelial sodium channel (ENaC), which can lead to salt-sensitive hypertension. Increased potassium intake, or a vegetarian diet, counteracts salt-sensitive hypertension, but the underlying mechanisms are not fully understood. Methods Bioinformatics and molecular modeling were used to identify G-quadruplex (G4) and their conformations in the SGK1 promoter. CD spectra and UV melting dynamics were measured to study the stability of G4 as influenced by potassium/sodium balance and resveratrol. RT-PCR and Western blot were employed to study the effects of potassium and resveratrol on the SGK1 isoform expression. Results The SGK1 gene encodes a G4 structure in the proximal upstream of promoter-2; the G4 structure is stabilized by potassium or resveratrol, but destabilized by sodium. Super-physiological levels of sodium stimulate the transcription of all SGK1 isoforms, whereas resveratrol or potassium supplementation inhibits the transcription of iso-2 and iso-3, but not iso-1. Conclusions Stabilizing the G4 by potassium or resveratrol induces alternative promoter usage and/or pre-mRNA splicing in the transcription of SGK1. General significance Potassium/sodium ion balance or resveratrol binding can act to regulate G4 molecular switches for controlling SGK1 gene expression, thereby presenting a new avenue for drug development.
@article{chen_g-quadruplex_2021,
	title = {A {G}-quadruplex nanoswitch in the {SGK1} promoter regulates isoform expression by {K}+/{Na}+ balance and resveratrol binding},
	volume = {1865},
	issn = {0304-4165},
	url = {http://www.sciencedirect.com/science/article/pii/S0304416520302890},
	doi = {10.1016/j.bbagen.2020.129778},
	abstract = {Background
High sodium intake can up-regulate the level of renal serum- and glucocorticoid-inducible kinase-1 (SGK1), which plays a pivotal role in controlling blood pressure via activation of the epithelial sodium channel (ENaC), which can lead to salt-sensitive hypertension. Increased potassium intake, or a vegetarian diet, counteracts salt-sensitive hypertension, but the underlying mechanisms are not fully understood.
Methods
Bioinformatics and molecular modeling were used to identify G-quadruplex (G4) and their conformations in the SGK1 promoter. CD spectra and UV melting dynamics were measured to study the stability of G4 as influenced by potassium/sodium balance and resveratrol. RT-PCR and Western blot were employed to study the effects of potassium and resveratrol on the SGK1 isoform expression.
Results
The SGK1 gene encodes a G4 structure in the proximal upstream of promoter-2; the G4 structure is stabilized by potassium or resveratrol, but destabilized by sodium. Super-physiological levels of sodium stimulate the transcription of all SGK1 isoforms, whereas resveratrol or potassium supplementation inhibits the transcription of iso-2 and iso-3, but not iso-1.
Conclusions
Stabilizing the G4 by potassium or resveratrol induces alternative promoter usage and/or pre-mRNA splicing in the transcription of SGK1.
General significance
Potassium/sodium ion balance or resveratrol binding can act to regulate G4 molecular switches for controlling SGK1 gene expression, thereby presenting a new avenue for drug development.},
	language = {en},
	number = {2},
	urldate = {2020-11-12},
	journal = {Biochimica et Biophysica Acta (BBA) - General Subjects},
	author = {Chen, Mengjie and Chen, Qi and Li, Yirui and Yang, Zhenjun and Taylor, Ethan W. and Zhao, Lijun},
	month = feb,
	year = {2021},
	note = {tex.ids= chenGquadruplexNanoswitchSGK12021},
	keywords = {Dietary sodium guidelines, G4, Gene expression, Salt-sensitive hypertension},
	pages = {129778},
}

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