Characterization of G-quadruplex formation in the ARID1A promoter

Yan, Ting; Zhao, Bo; Wu, Qiong; Wang, Wenmeng; Shi, Jinming; Li, Dangdang; Stovall, Daniel B.; Sui, Guangchao

doi:10.1016/j.ijbiomac.2020.01.210

Cited by 12 publications

(10 citation statements)

References 60 publications

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“…Our studies indicated that compared to the feature maps of mutants, WT oligonucleotides could effectively form the stable parallel G4 structures in vitro. Furthermore, related reports indicated that G-tracts also had weak potential to form unstable G4 structures in the presence of two G bases or far from more than seven nucleotides, which explained that the mutants could still detect the characteristic molar ellipticity at 240 and 260 nm. ,, …”

Section: Discussionmentioning

confidence: 97%

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G-Quadruplex Structures as a “Switch” Regulate ATF4 Expression in Ferroptotic HepG2 Cells

et al. 2023

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G-quadruplex (G4) is a noncanonical structure folded in a widespread manner by guanine-rich tandem repeated sequences. As a key response factor, activating transcription factor 4 (ATF4) has dual functions in managing iron-dependent ferroptosis by regulating amino acid synthesis and antioxidant-related gene expression. In our study, the activity of ATF4 expression was elevated in HepG2 cells induced by erastin. Based on preliminary bioinformatics analyses, the G-tract region, named WT, had high potential to form G4, and it was found that PDS could markedly weaken the increase of ATF4 expression by reducing the sensitivity of HepG2 cells toward erastin. In circular dichroism spectra, WT oligonucleotides showed characteristic molar ellipticity at specific wavelengths of parallel G4 structures, while corresponding single-base mutants possessed a weaker ability to form G4, which were consistent with immunostaining results. In addition, endogenous G4 formed by the WT motif was significantly destroyed in HepG2 cells treated with erastin. After being transfected with WT oligonucleotides, the levels of ATF4 mRNA decreased significantly regardless of being treated with erastin or not. Meanwhile, mutations of G-tracts could advantageously impact the luciferase expression downstream of an ATF4 promoter in reporter assays, manifesting that the decrease of endogenous G4 in the ATF4 promoter was positively associated with the expression enhanced by erastin in HepG2 cells.

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Section: Discussionmentioning

confidence: 97%

“…To detect the G-quadruplex formed by oligonucleotides in HepG2 cells, immunostaining and fluorescence microscopy were performed as previously described . HepG2 cells were inoculated into a 6-well plate until it reached about a confluency of 60–80%.…”

Section: Methodsmentioning

confidence: 99%

G-Quadruplex Structures as a “Switch” Regulate ATF4 Expression in Ferroptotic HepG2 Cells

et al. 2023

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“…2b). In addition, it was observed that P2 lost the G4 structural conformation in the presence of Li + ion, an ion known to destabilize the G-quadruplex structure 61,62 . These results suggest that P2 may preferentially adopt a hybrid G4 structure in the presence of K + over Na + and the structure is disrupted in the presence of Li + .…”

Section: A Stable Intramolecular Mtor G-quadruplexmentioning

confidence: 99%

Putative G-quadruplex Formation in the Upstream Region of mTOR Gene

Fatma

Saha

Das

2022

Preprint

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The mammalian target of rapamycin (mTOR) and its signaling pathways are highly critical for maintaining cell homeostasis. The mTOR signaling pathway is often hyperactivated in many types of cancers making it an attractive therapeutic target for cancer. The efficacy of current mTOR protein inhibitors in therapy has seen limited success. The search for alternative means of therapy may lie in the regulation of mTOR gene expression using DNA structures. In the current study, we explore and report the presence of a novel G4 structure in the upstream region of mTOR gene. We have demonstrated the G-quadruplex formation in the mTOR G4 region using biophysical experiments. This study paves the way for the design of novel selective DNA G4 binders for mTOR G4 for anticancer therapeutics.

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“…Among the oncogene promoter G4 motifs examined so far, most of them including the promoter G4 motifs of c‐Myc, c‐Kit, RET, Hif‐1α, PDGF‐A, hTERT, VEGF (Brooks et al ., 2010), HoxC10 (Zhang et al ., 2018a), and SNAIL1 (Wang et al ., 2020) act as silencers to downregulate the corresponding oncogenes. Only the promoter G4 motifs of BCL‐2 (Brooks et al ., 2010), BAP1 (Li et al ., 2018) and ARID1A (Yan et al ., 2020) function as enhancers to upregulate the 3 oncogenes. It remains unclear whether and how P450s of any species acquire and retain G4 motifs to adjust their expression in response to xenobiotic signals.…”

Section: Introductionmentioning

confidence: 99%

A transposon‐introduced G‐quadruplex motif is selectively retained and constrained to downregulate CYP321A1

et al. 2022

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Insects utilize xenobiotic compounds to up-and downregulate cytochrome P450 monooxygenases (P450s) involved in detoxification of toxic xenobiotics including phytochemicals and pesticides. G-quadruplexes (G4)-forming DNA motifs are enriched in the promoter regions of transcription factors and function as cis-acting elements to regulate these genes. Whether and how P450s gain and keep G4 DNA motifs to regulate their expression still remain unexplored. Here, we show that CYP321A1, a xenobioticmetabolizing P450 from Helicoverpa zea, a polyphagous insect of economic importance, has acquired and preserved a G4 DNA motif by selectively retaining a transposon known as HzIS1-3 that carries this G4 DNA motif in its promoter region. The HzIS1-3 G4 DNA motif acts as a silencer to suppress the constitutive and induced expression of CYP321A1 by plant allelochemicals flavone and xanthotoxin through folding into an intramolecular parallel or hybrid-1 conformation in the absence or presence of K + . The G4 ligand Nmethylmesoporphyrin IX (NMM) strengthens the silencing effect of HzIS1-3 G4 DNA motif by switching its structure from hybrid-1 to hybrid-2. The enrichment of transposons in P450s and other environment-adaptation genes implies that selective retention of G4 DNA motif-carrying transposons may be the main evolutionary route for these genes to obtain G4 DNA motifs.

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Characterization of G-quadruplex formation in the ARID1A promoter

Cited by 12 publications

References 60 publications

G-Quadruplex Structures as a “Switch” Regulate ATF4 Expression in Ferroptotic HepG2 Cells

G-Quadruplex Structures as a “Switch” Regulate ATF4 Expression in Ferroptotic HepG2 Cells

Putative G-quadruplex Formation in the Upstream Region of mTOR Gene

A transposon‐introduced G‐quadruplex motif is selectively retained and constrained to downregulate CYP321A1

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