Composite 5-methylations of cytosines modulate i-motif stability in a sequence-specific manner: Implications for DNA nanotechnology and epigenetic regulation of plant telomeric DNA

This publication doesn't include Faculty of Arts. It includes Central European Institute of Technology. Official publication website can be found on muni.cz.

Authors

ŠKOLÁKOVÁ Petra BADRI Zahra TRANTÍRKOVÁ Silvie RYNEŠ Jan ŠPONER Jiří FOJTOVÁ Miloslava FAJKUS Jiří MAREK Radek VORLÍČKOVÁ Michaela MERGNY Jean-Louis TRANTÍREK Lukáš

Year of publication 2020
Type Article in Periodical
Magazine / Source BBA - General Subjects
MU Faculty or unit

Central European Institute of Technology

Citation
Web DOI: 10.1016/j.bbagen.2020.129651
Doi http://dx.doi.org/10.1016/j.bbagen.2020.129651
Keywords i-motif;DNA;Epigenetic modification;DNA nanotechnology;Plant telomeric DNA;Cytosine methylation
Attached files
Description Background: The i-motif is a tetrameric DNA structure based on the formation of hemiprotonated cytosinecytosine (C+.C) base pairs. i-motifs are widely used in nanotechnology. In biological systems, i-motifs are involved in gene regulation and in control of genome integrity. In vivo, the i-motif forming sequences are subjects of epigenetic modifications, particularly 5-cytosine methylation. In plants, natively occurring methylation patterns lead to a complex network of C+.C, 5mC+.C and 5mC+.5mC base-pairs in the i-motif stem. The impact of complex methylation patterns (CMPs) on i-motif formation propensity is currently unknown. Methods: We employed CD and UV-absorption spectroscopies, native PAGE, thermal denaturation and quantumchemical calculations to analyse the effects of native, native-like, and non-native CMPs in the i-motif stem on the i-motif stability and pKa. Results: CMPs have strong influence on i-motif stability and pKa and influence these parameters in sequencespecific manner. In contrast to a general belief, i) CMPs do not invariably stabilize the i-motif, and ii) when the CMPs do stabilize the i-motif, the extent of the stabilization depends (in a complex manner) on the number and pattern of symmetric 5mC+.5mC or asymmetric 5mC+.C base pairs in the i-motif stem. Conclusions: CMPs can be effectively used to fine-tune i-motif properties. Our data support the notion of epigenetic modifications as a plausible control mechanism of i-motif formation in vivo. General Significance: Our results have implications in epigenetic regulation of telomeric DNA in plants and highlight the potential and limitations of engineered patterning of cytosine methylations on the i-motif scaffold in nanotechnological applications.
Related projects: