Hairpin-bisulfite sequencing of cells exposed to decitabine documents the process of DNA demethylation

Although the mechanism of DNA demethylating drugs has been understood for many years, the direct effect of these drugs on methylation of the complementary strands of DNA has not been formally demonstrated. By using hairpin-bisulphite sequencing, we describe the kinetics and pattern of DNA methylatio...

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Bibliographic Details
Published in:Epigenetics 2021-11, Vol.16 (11), p.1251-1259
Main Authors: Mayyas, Issam M, Weeks, Robert J, Day, Robert C, Magrath, Helena E, O'Connor, Karina M, Kardailsky, Olga, Hore, Timothy A, Hampton, Mark B, Morison, Ian M
Format: Article
Language:English
Subjects:
Azacitidine
Decitabine
Demethylation
DNA (Cytosine-5-)-Methyltransferase 1
DNA (Cytosine-5-)-Methyltransferases - metabolism
DNA Demethylation
DNA Methylation
dnmt1 inhibition
Humans
Research Paper
Sulfites
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Summary:Although the mechanism of DNA demethylating drugs has been understood for many years, the direct effect of these drugs on methylation of the complementary strands of DNA has not been formally demonstrated. By using hairpin-bisulphite sequencing, we describe the kinetics and pattern of DNA methylation following treatment of cells by the DNA methyltransferase 1 (DNMT1) inhibitor, decitabine. As expected, we demonstrate complete loss of methylation on the daughter strand following S-phase in selected densely methylated genes in synchronized Jurkat cells. Thereafter, cells showed a heterogeneous pattern of methylation reflecting replication of the unmethylated strand and restoration of methylation.
ISSN:1559-2294
1559-2308
DOI:10.1080/15592294.2020.1861169