DNA hydroxymethylation increases the susceptibility of reactivation of methylated alleles in cancer cells.

Epigenetics

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Division of Etiology, Peking University Cancer Hospital and Institute, Beijing, China.

Published: May 2021

AI Article Synopsis

  • The study highlights how 5-methylcytosine (5mC) in mammalian DNA can be oxidized by TET enzymes to form 5-hydroxymethylcytosine (5hmC) and other derivatives, which are important for DNA demethylation.
  • While some 5hmC remains stable in the genome and helps maintain chromatin flexibility, its direct impact on gene transcription is not fully understood.
  • The researchers engineered a zinc-finger protein-based DNA dioxygenase (P16-TET) to enhance hydroxymethylation in cancer cells, discovering that while hydroxymethylated alleles are inactive, this modification may increase the likelihood of reactivating dormant methylated alleles.

Article Abstract

It is well established that 5-methylcytosine (5mC) in genomic DNA of mammalian cells can be oxidized into 5-hydroxymethylcytosine (5hmC) and other derivates by DNA dioxygenase TETs. While conversion of 5mC to 5hmC plays an important role in active DNA demethylation through further oxidation steps, a certain proportion of 5hmCs remain in the genome. Although 5hmCs contribute to the flexibility of chromatin and protect bivalent promoters from hypermethylation, the direct effect of 5hmCs on gene transcription is unknown. In this present study, we have engineered a zinc-finger protein-based P16-specific DNA dioxygenase (P16-TET) to induce hydroxymethylation and demethylation in cancer cells. Our results demonstrate, for the first time, that although the hydroxymethylated alleles retain transcriptionally inactive, hydroxymethylation could increase the susceptibility of reactivation of methylated alleles.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574387PMC
http://dx.doi.org/10.1080/15592294.2019.1700004DOI Listing

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