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Epigenetic TET-Catalyzed Oxidative Products of 5-Methylcytosine Impede Z-DNA Formation of CG Decamers

[Image: see text] Methylation of cytosine has been known to play a significant role in epigenetic regulation. 5-Methylcytosine was among the first base modification that was discovered for the capability to facilitate B/Z-DNA transition as observed in CG repeated tracks. A study on gene repression b...

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Autores principales: Vongsutilers, Vorasit, Shinohara, Yoko, Kawai, Gota
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2020
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161056/
https://www.ncbi.nlm.nih.gov/pubmed/32309715
http://dx.doi.org/10.1021/acsomega.0c00120
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author Vongsutilers, Vorasit
Shinohara, Yoko
Kawai, Gota
author_facet Vongsutilers, Vorasit
Shinohara, Yoko
Kawai, Gota
author_sort Vongsutilers, Vorasit
collection PubMed
description [Image: see text] Methylation of cytosine has been known to play a significant role in epigenetic regulation. 5-Methylcytosine was among the first base modification that was discovered for the capability to facilitate B/Z-DNA transition as observed in CG repeated tracks. A study on gene repression by Z-DNA prone sequence as in ADAM-12 has ignited our research interest for the Z-DNA role in epigenetics. Ten eleven translocation family proteins are responsible to catalyze 5-methylcytosine to produce oxidative products including 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxycytosine, which each may have unique function rather than the sole purpose of 5-methylcytosine clearance. Although the Z-DNA-promoting effect of 5-methylcytosine was well established, the effect of its oxidative products on Z-DNA remain unknown. In this study, the Z-DNA-promoting effect of 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxycytosine on the CG decamer model were investigated along with known Z-DNA stabilizers, 5-methylcytosine and 8-oxoguanine. Experimental results from circular dichroism (CD) and NMR indicates that all oxidative products of 5-methylcytosine hinder B/Z-DNA transition as high salt concentration suitable to stabilize and convert unmodified CG decamer to Z-DNA conformation is insufficient to facilitate the B/Z-DNA transition of CG decamer containing 5-hydroxymethylcytosine, 5-formylcytosine, or 5-carboxycytosine. Molecular dynamic simulation and free energy calculation by MM-PBSA are in agreement with the experimental finding that 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxycytosine destabilize Z-DNA conformation of CG decamer, in contrast to its precursor. Investigation of Z-DNA switch-on/switch-off regulated by 5-methylcytosine and its oxidative products is a further step to elucidate the potential of epigenetic regulated via Z-DNA.
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spelling pubmed-71610562020-04-17 Epigenetic TET-Catalyzed Oxidative Products of 5-Methylcytosine Impede Z-DNA Formation of CG Decamers Vongsutilers, Vorasit Shinohara, Yoko Kawai, Gota ACS Omega [Image: see text] Methylation of cytosine has been known to play a significant role in epigenetic regulation. 5-Methylcytosine was among the first base modification that was discovered for the capability to facilitate B/Z-DNA transition as observed in CG repeated tracks. A study on gene repression by Z-DNA prone sequence as in ADAM-12 has ignited our research interest for the Z-DNA role in epigenetics. Ten eleven translocation family proteins are responsible to catalyze 5-methylcytosine to produce oxidative products including 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxycytosine, which each may have unique function rather than the sole purpose of 5-methylcytosine clearance. Although the Z-DNA-promoting effect of 5-methylcytosine was well established, the effect of its oxidative products on Z-DNA remain unknown. In this study, the Z-DNA-promoting effect of 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxycytosine on the CG decamer model were investigated along with known Z-DNA stabilizers, 5-methylcytosine and 8-oxoguanine. Experimental results from circular dichroism (CD) and NMR indicates that all oxidative products of 5-methylcytosine hinder B/Z-DNA transition as high salt concentration suitable to stabilize and convert unmodified CG decamer to Z-DNA conformation is insufficient to facilitate the B/Z-DNA transition of CG decamer containing 5-hydroxymethylcytosine, 5-formylcytosine, or 5-carboxycytosine. Molecular dynamic simulation and free energy calculation by MM-PBSA are in agreement with the experimental finding that 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxycytosine destabilize Z-DNA conformation of CG decamer, in contrast to its precursor. Investigation of Z-DNA switch-on/switch-off regulated by 5-methylcytosine and its oxidative products is a further step to elucidate the potential of epigenetic regulated via Z-DNA. American Chemical Society 2020-03-31 /pmc/articles/PMC7161056/ /pubmed/32309715 http://dx.doi.org/10.1021/acsomega.0c00120 Text en Copyright © 2020 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Vongsutilers, Vorasit
Shinohara, Yoko
Kawai, Gota
Epigenetic TET-Catalyzed Oxidative Products of 5-Methylcytosine Impede Z-DNA Formation of CG Decamers
title Epigenetic TET-Catalyzed Oxidative Products of 5-Methylcytosine Impede Z-DNA Formation of CG Decamers
title_full Epigenetic TET-Catalyzed Oxidative Products of 5-Methylcytosine Impede Z-DNA Formation of CG Decamers
title_fullStr Epigenetic TET-Catalyzed Oxidative Products of 5-Methylcytosine Impede Z-DNA Formation of CG Decamers
title_full_unstemmed Epigenetic TET-Catalyzed Oxidative Products of 5-Methylcytosine Impede Z-DNA Formation of CG Decamers
title_short Epigenetic TET-Catalyzed Oxidative Products of 5-Methylcytosine Impede Z-DNA Formation of CG Decamers
title_sort epigenetic tet-catalyzed oxidative products of 5-methylcytosine impede z-dna formation of cg decamers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161056/
https://www.ncbi.nlm.nih.gov/pubmed/32309715
http://dx.doi.org/10.1021/acsomega.0c00120
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