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Structural dynamics of double-stranded DNA with epigenome modification
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DOI：10.1093/nar/gkaa1210.png)
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Abstract
En 中文
Modification of cytosine plays an important role in epigenetic regulation of gene expression and genome stability. Cytosine is converted to 5-methylcytosine (5mC) by DNA methyltransferase; in turn, 5mC may be oxidized to 5-hydroxymethylcytosine (5hmC) by ten-eleven translocation enzyme. The structural flexibility of DNA is known to affect the binding of proteins to methylated DNA. Here, we have carried out a semiquantitative analysis of the dynamics of double-stranded DNA (dsDNA) containing various epigenetic modifications by combining data from imino H-1 exchange and imino H-1 R-1 rho, relaxation dispersion NMR experiments in a complementary way. Using this approach, we characterized the base-opening (k(open)) and base-closing (k(close)) rates, facilitating a comparison of the base-opening and -closing process of dsDNA containing cytosine in different states of epigenetic modification. A particularly striking result is the increase in the k(open )rate of hemimethylated dsDNA 5mC/C relative to unmodified or fully methylated dsDNA, indicating that the Watson- Crick base pairs undergo selective destabilization in 5mC/C. Collectively, our findings imply that the epigenetic modulation of cytosine dynamics in dsDNA mediates destabilization of the GC Watson-Crick base pair to allow base-flipping in living cells.
Keywords:
HOOGSTEEN BASE-PAIRS
SOFTWARE PACKAGE
PROTON-EXCHANGE
IMINO PROTON
METHYLATION
5-FORMYLCYTOSINE
VISUALIZATION
MECHANISMS
PROTEINS
SYSTEM
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