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= chenGquadruplexNanoswitchSGK12021Paper 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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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":[{"propositions":[],"lastnames":["Chen"],"firstnames":["Mengjie"],"suffixes":[]},{"propositions":[],"lastnames":["Chen"],"firstnames":["Qi"],"suffixes":[]},{"propositions":[],"lastnames":["Li"],"firstnames":["Yirui"],"suffixes":[]},{"propositions":[],"lastnames":["Yang"],"firstnames":["Zhenjun"],"suffixes":[]},{"propositions":[],"lastnames":["Taylor"],"firstnames":["Ethan","W."],"suffixes":[]},{"propositions":[],"lastnames":["Zhao"],"firstnames":["Lijun"],"suffixes":[]}],"month":"February","year":"2021","note":"tex.ids= chenGquadruplexNanoswitchSGK12021","keywords":"Dietary sodium guidelines, G4, Gene expression, Salt-sensitive hypertension","pages":"129778","bibtex":"@article{chen_g-quadruplex_2021,\n\ttitle = {A {G}-quadruplex nanoswitch in the {SGK1} promoter regulates isoform expression by {K}+/{Na}+ balance and resveratrol binding},\n\tvolume = {1865},\n\tissn = {0304-4165},\n\turl = {http://www.sciencedirect.com/science/article/pii/S0304416520302890},\n\tdoi = {10.1016/j.bbagen.2020.129778},\n\tabstract = {Background\nHigh 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.\nMethods\nBioinformatics 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.\nResults\nThe 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.\nConclusions\nStabilizing the G4 by potassium or resveratrol induces alternative promoter usage and/or pre-mRNA splicing in the transcription of SGK1.\nGeneral significance\nPotassium/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.},\n\tlanguage = {en},\n\tnumber = {2},\n\turldate = {2020-11-12},\n\tjournal = {Biochimica et Biophysica Acta (BBA) - General Subjects},\n\tauthor = {Chen, Mengjie and Chen, Qi and Li, Yirui and Yang, Zhenjun and Taylor, Ethan W. and Zhao, Lijun},\n\tmonth = feb,\n\tyear = {2021},\n\tnote = {tex.ids= chenGquadruplexNanoswitchSGK12021},\n\tkeywords = {Dietary sodium guidelines, G4, Gene expression, Salt-sensitive hypertension},\n\tpages = {129778},\n}\n\n","author_short":["Chen, M.","Chen, Q.","Li, Y.","Yang, Z.","Taylor, E. W.","Zhao, L."],"key":"chen_g-quadruplex_2021","id":"chen_g-quadruplex_2021","bibbaseid":"chen-chen-li-yang-taylor-zhao-agquadruplexnanoswitchinthesgk1promoterregulatesisoformexpressionbyknabalanceandresveratrolbinding-2021","role":"author","urls":{"Paper":"http://www.sciencedirect.com/science/article/pii/S0304416520302890"},"keyword":["Dietary sodium guidelines","G4","Gene expression","Salt-sensitive hypertension"],"metadata":{"authorlinks":{}},"html":""},"bibtype":"article","biburl":"https://bibbase.org/zotero/eric.larG4","dataSources":["4i5C7S78DvJNsaHyg","5L2zM5wNE5CBYNuea"],"keywords":["dietary sodium guidelines","g4","gene expression","salt-sensitive hypertension"],"search_terms":["quadruplex","nanoswitch","sgk1","promoter","regulates","isoform","expression","balance","resveratrol","binding","chen","chen","li","yang","taylor","zhao"],"title":"A G-quadruplex nanoswitch in the SGK1 promoter regulates isoform expression by K+/Na+ balance and resveratrol binding","year":2021}