i-motif structures in long cytosine-rich sequences found upstream of the promoter region of the SMARCA4 gene

Benabou, Sanae; Aviñó, Anna; Lyonnais, Sébastien; González, Carlos; Eritja, Ramón; Juan, Anna de; Gargallo, Raimundo

doi:10.1016/j.biochi.2017.06.005

Cited by 14 publications

(13 citation statements)

References 51 publications

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“…The in vitro formation of i-motif structures in DNA sequences corresponding to centromeres, telomeres and to the promoter regions of several oncogenes has been demonstrated [13][14][15] . Recently, a new study provided the first direct evidence for the presence in vivo of i-motif structures in human cells and control regulatory functions 16 .…”

Section: Introductionmentioning

confidence: 99%

Study of light-induced formation of photodimers in the i-motif nucleic acid structure by rapid-scan FTIR difference spectroscopy and hybrid hard- and soft-modelling

Benabou

Ruckebusch

Sliwa

et al. 2018

Phys. Chem. Chem. Phys.

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The i-motif is a DNA structure formed by cytosine-rich sequences, very relevant from a biochemical point of view and potentially useful in nanotechnology as pH-sensitive nanodevices or nanomotors. To provide a different view on the structural changes and dynamics of direct excitation processes involving i-motif structures, the use of rapid-scan FTIR spectroscopy is proposed. Hybrid hard- and soft-modelling based on the Multivariate Curve Resolution by Alternating Least Squares (MCR-ALS) algorithm has been used for the resolution of rapid-scan FTIR spectra and the interpretation of the photochemically induced time-dependent conformational changes of i-motif structures. The hybrid hard- and soft-modelling version of MCR-ALS (HS-MCR), which allows the introduction of kinetic models to describe process behavior, provides also rate constants associated with the transitions modeled. The results show that UV irradiation does not produce degradation of the studied sequences but induces the formation of photodimers. The presence of these affect much more the stability of i-motif structures formed by short sequences than that of those formed by longer sequences containing additional structural stabilizing elements, such as hairpins.

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Section: Introductionmentioning

confidence: 99%

Study of light-induced formation of photodimers in the i-motif nucleic acid structure by rapid-scan FTIR difference spectroscopy and hybrid hard- and soft-modelling

Benabou

Ruckebusch

Sliwa

et al. 2018

Phys. Chem. Chem. Phys.

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“…In a first step the solution equilibria of a cytosine-rich sequence were studied 16 . This sequence (identified by us as SMC01) is composed by 44 nucleotides and contains six tracts of cytosine bases.…”

Section: Discussionmentioning

confidence: 99%

“…In the promoter region of this gene there is a wealth of cytosine or guanine bases that could lead to the formation of folded structures, such as i-motif or G-quadruplex, respectively. In a previous work, we studied a 44-nucleotides long cytosine-rich sequence present near the promoter region (identified by us as SMC01) and proposed the formation of i-motif structures within it 16 . Here, we focused our attention on the study of the guanine-rich sequence complementary to SMC01 (SMG01, Fig.…”

Section: Introductionmentioning

confidence: 99%

A pH-dependent bolt involving cytosine bases located in the lateral loops of antiparallel G-quadruplex structures within the SMARCA4 gene promotor

Benabou

Mazzini

Aviñó

et al. 2019

Sci Rep

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Some lung and ovarian tumors are connected to the loss of expression of SMARCA4 gene. In its promoter region, a 44-nucleotides long guanine sequence prone to form G-quadruplex structures has been studied by means of spectroscopic techniques (circular dichroism, molecular absorption and nuclear magnetic resonance), size exclusion chromatography and multivariate analysis. The results have shown that the central 21-nucleotides long sequence comprising four guanine tracts of disparate length is able to fold into a pH-dependent ensemble of G-quadruplex structures. Based on acid-base titrations and melting experiments of wild and mutated sequences, the formation of a c•c + base pair between cytosine bases present at the two lateral loops is shown to promote a reduction in conformational heterogeneity, as well as an increase in thermal stability. The formation of this base pair is characterized by a pK a value of 7.1 ± 0.2 at 20 °C and 150 mM KCl. This value, higher than those usually found in i-motif structures, is related to the additional stability provided by guanine tetrads in the G-quadruplex. To our knowledge, this is the first thermodynamic description of this base pair in loops of antiparallel G-quadruplex structures. Nucleic acids can adopt structures other than the Watson-Crick double helix, such as the i-motif or G-quadruplex structures with biologically relevant roles. The i-motif is formed within cytosine-rich (C-rich) sequences, being its building block the C•C + base pair. As the protonation of some cytosine bases is needed for its formation, the overall stability of the i-motif structure is strongly dependent on pH 1,2. Because of this fact, the potential role in vivo of i-motif structures is still under investigation 3,4. On the other hand, G-quadruplexes are formed by DNA or RNA sequences that are particularly rich in guanine bases. The building block of these structures is the G-quartet (or G-tetrad), which consist on four guanine bases held together by Hoogsteen-type hydrogen bonds in a planar arrangement (Fig. 1a). G-quadruplex structures are mainly stabilized by intramolecular or intermolecular stacking of these G-quartets, as well as by electrostatic interactions with cations (such as K + or Na +) placed within the structure. G-quadruplex structure variability depends strongly on the length of the guanine tracks, the loops connecting the stacked G-quartets, the syn/anti preference of the purine bases, and the presence of ligands or modifiers. Hence, G-quadruplexes may be classified into 'antiparallel' , 'parallel' or even 'hybrid' arrangements (Fig. 1b) 5. The in vitro formation of such structures in DNA sequences corresponding to the end of telomeres and to the promoter regions of several oncogenes has previously been shown, as well as their in vivo presence 6,7. Hence, the role of G-quadruplex structures in biological processes like cancer or aging seems to be clear 8-12. Accordingly, research is being made to identify ligands that could selectively bind to G-quadruplex structures to modulate g...

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“…Additionally, the ATP-dependent chromatin remodeler SMARCA4 , frequently mutated and downexpressed in ovarian and lung cancer [ 162 ], contains a C-rich region from −71 to −28 nt upstream of its promoter. Structurally, this region contains one tract with four cytosines, three tracts with three, and two tracts with two, forming a relatively stable and homogeneous intramolecular i-Motif in terms of both pH and temperature [ 58 ]. Future studies might reveal if i-Motifs in RB and SMARCA4 could provide new mechanisms for the modulation of gene expression.…”

Section: Relevant Quadruplex Structures Involved In Cancermentioning

confidence: 99%

An Updated Focus on Quadruplex Structures as Potential Therapeutic Targets in Cancer

Sánchez-Martín

López-Pujante

Soriano

et al. 2020

IJMS

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Non-canonical, four-stranded nucleic acids secondary structures are present within regulatory regions in the human genome and transcriptome. To date, these quadruplex structures include both DNA and RNA G-quadruplexes, formed in guanine-rich sequences, and i-Motifs, found in cytosine-rich sequences, as their counterparts. Quadruplexes have been extensively associated with cancer, playing an important role in telomere maintenance and control of genetic expression of several oncogenes and tumor suppressors. Therefore, quadruplex structures are considered attractive molecular targets for cancer therapeutics with novel mechanisms of action. In this review, we provide a general overview about recent research on the implications of quadruplex structures in cancer, firstly gathering together DNA G-quadruplexes, RNA G-quadruplexes as well as DNA i-Motifs.

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i-motif structures in long cytosine-rich sequences found upstream of the promoter region of the SMARCA4 gene

Cited by 14 publications

References 51 publications

Study of light-induced formation of photodimers in the i-motif nucleic acid structure by rapid-scan FTIR difference spectroscopy and hybrid hard- and soft-modelling

Study of light-induced formation of photodimers in the i-motif nucleic acid structure by rapid-scan FTIR difference spectroscopy and hybrid hard- and soft-modelling

A pH-dependent bolt involving cytosine bases located in the lateral loops of antiparallel G-quadruplex structures within the SMARCA4 gene promotor

An Updated Focus on Quadruplex Structures as Potential Therapeutic Targets in Cancer

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