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DNA methylation on N(6)-adenine in mammalian embryonic stem cells
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DNA methylation on N(6)-adenine in mammalian embryonic stem cells
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DNA methylation on N(6)-adenine in mammalian embryonic stem cells
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Journal Article
DNA methylation on N(6)-adenine in mammalian embryonic stem cells
2016
Overview
It has been widely accepted that 5-methylcytosine is the only form of DNA methylation in mammalian genomes. Here we identify N(6)-methyladenine as another form of DNA modification in mouse embryonic stem cells. Alkbh1 encodes a demethylase for N(6)-methyladenine. An increase of N(6)-methyladenine levels in Alkbh1-deficient cells leads to transcriptional silencing. N(6)-methyladenine deposition is inversely correlated with the evolutionary age of LINE-1 transposons; its deposition is strongly enriched at young (<1.5 million years old) but not old (>6 million years old) L1 elements. The deposition of N(6)-methyladenine correlates with epigenetic silencing of such LINE-1 transposons, together with their neighbouring enhancers and genes, thereby resisting the gene activation signals during embryonic stem cell differentiation. As young full-length LINE-1 transposons are strongly enriched on the X chromosome, genes located on the X chromosome are also silenced. Thus, N(6)-methyladenine developed a new role in epigenetic silencing in mammalian evolution distinct from its role in gene activation in other organisms. Our results demonstrate that N(6)-methyladenine constitutes a crucial component of the epigenetic regulation repertoire in mammalian genomes.
Subject
Adenine - analogs & derivatives
/ AlkB Homolog 1, Histone H2a Dioxygenase
/ Animals
/ Cell Differentiation - genetics
/ DNA Transposable Elements - genetics
/ DNA-(Apurinic or Apyrimidinic Site) Lyase - deficiency
/ DNA-(Apurinic or Apyrimidinic Site) Lyase - genetics
/ DNA-(Apurinic or Apyrimidinic Site) Lyase - metabolism
/ Enhancer Elements, Genetic - genetics
/ Epigenesis, Genetic - genetics
/ Long Interspersed Nucleotide Elements - genetics
/ Mice
/ Mouse Embryonic Stem Cells - cytology
