Combined Effects of Methylated Cytosine and Molecular Crowding on the Thermodynamic Stability of DNA Duplexes
Methylated cytosine within CpG dinucleotides is a key factor for epigenetic gene regulation. It has been revealed that methylated cytosine decreases DNA backbone flexibility and increases the thermal stability of DNA. Although the molecular environment is an important factor for the structure, therm...
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MDPI AG
2021-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/2/947 |
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| author | Mitsuki Tsuruta Yui Sugitani Naoki Sugimoto Daisuke Miyoshi |
| author_facet | Mitsuki Tsuruta Yui Sugitani Naoki Sugimoto Daisuke Miyoshi |
| author_sort | Mitsuki Tsuruta |
| collection | DOAJ |
| description | Methylated cytosine within CpG dinucleotides is a key factor for epigenetic gene regulation. It has been revealed that methylated cytosine decreases DNA backbone flexibility and increases the thermal stability of DNA. Although the molecular environment is an important factor for the structure, thermodynamics, and function of biomolecules, there are few reports on the effects of methylated cytosine under a cell-mimicking molecular environment. Here, we systematically investigated the effects of methylated cytosine on the thermodynamics of DNA duplexes under molecular crowding conditions, which is a critical difference between the molecular environment in cells and test tubes. Thermodynamic parameters quantitatively demonstrated that the methylation effect and molecular crowding effect on DNA duplexes are independent and additive, in which the degree of the stabilization is the sum of the methylation effect and molecular crowding effect. Furthermore, the effects of methylation and molecular crowding correlate with the hydration states of DNA duplexes. The stabilization effect of methylation was due to the favorable enthalpic contribution, suggesting that direct interactions of the methyl group with adjacent bases and adjacent methyl groups play a role in determining the flexibility and thermodynamics of DNA duplexes. These results are useful to predict the properties of DNA duplexes with methylation in cell-mimicking conditions. |
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| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T04:20:49Z |
| publishDate | 2021-01-01 |
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| spelling | doaj.art-4ed6202ee2fe4a3d92b3ac73368d57752023-12-03T13:47:47ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-01-0122294710.3390/ijms22020947Combined Effects of Methylated Cytosine and Molecular Crowding on the Thermodynamic Stability of DNA DuplexesMitsuki Tsuruta0Yui Sugitani1Naoki Sugimoto2Daisuke Miyoshi3Faculty of Frontiers of Innovative Research in Science and Technology (FIRST), Konan University, Kobe 650-0047, JapanFaculty of Frontiers of Innovative Research in Science and Technology (FIRST), Konan University, Kobe 650-0047, JapanFaculty of Frontiers of Innovative Research in Science and Technology (FIRST), Konan University, Kobe 650-0047, JapanFaculty of Frontiers of Innovative Research in Science and Technology (FIRST), Konan University, Kobe 650-0047, JapanMethylated cytosine within CpG dinucleotides is a key factor for epigenetic gene regulation. It has been revealed that methylated cytosine decreases DNA backbone flexibility and increases the thermal stability of DNA. Although the molecular environment is an important factor for the structure, thermodynamics, and function of biomolecules, there are few reports on the effects of methylated cytosine under a cell-mimicking molecular environment. Here, we systematically investigated the effects of methylated cytosine on the thermodynamics of DNA duplexes under molecular crowding conditions, which is a critical difference between the molecular environment in cells and test tubes. Thermodynamic parameters quantitatively demonstrated that the methylation effect and molecular crowding effect on DNA duplexes are independent and additive, in which the degree of the stabilization is the sum of the methylation effect and molecular crowding effect. Furthermore, the effects of methylation and molecular crowding correlate with the hydration states of DNA duplexes. The stabilization effect of methylation was due to the favorable enthalpic contribution, suggesting that direct interactions of the methyl group with adjacent bases and adjacent methyl groups play a role in determining the flexibility and thermodynamics of DNA duplexes. These results are useful to predict the properties of DNA duplexes with methylation in cell-mimicking conditions.https://www.mdpi.com/1422-0067/22/2/947methylated cytosinemolecular crowdingosmolyteepigeneticsthermodynamics |
| spellingShingle | Mitsuki Tsuruta Yui Sugitani Naoki Sugimoto Daisuke Miyoshi Combined Effects of Methylated Cytosine and Molecular Crowding on the Thermodynamic Stability of DNA Duplexes International Journal of Molecular Sciences methylated cytosine molecular crowding osmolyte epigenetics thermodynamics |
| title | Combined Effects of Methylated Cytosine and Molecular Crowding on the Thermodynamic Stability of DNA Duplexes |
| title_full | Combined Effects of Methylated Cytosine and Molecular Crowding on the Thermodynamic Stability of DNA Duplexes |
| title_fullStr | Combined Effects of Methylated Cytosine and Molecular Crowding on the Thermodynamic Stability of DNA Duplexes |
| title_full_unstemmed | Combined Effects of Methylated Cytosine and Molecular Crowding on the Thermodynamic Stability of DNA Duplexes |
| title_short | Combined Effects of Methylated Cytosine and Molecular Crowding on the Thermodynamic Stability of DNA Duplexes |
| title_sort | combined effects of methylated cytosine and molecular crowding on the thermodynamic stability of dna duplexes |
| topic | methylated cytosine molecular crowding osmolyte epigenetics thermodynamics |
| url | https://www.mdpi.com/1422-0067/22/2/947 |
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