Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

National Institute of Environmental Health Sciences

Use this QR code to view the newest version of this document
Use this QR code to view the newest version of this document

Your Environment. Your Health.

Publication Detail

Title: DNA methylation on N(6)-adenine in mammalian embryonic stem cells.

Authors: Wu, Tao P; Wang, Tao; Seetin, Matthew G; Lai, Yongquan; Zhu, Shijia; Lin, Kaixuan; Liu, Yifei; Byrum, Stephanie D; Mackintosh, Samuel G; Zhong, Mei; Tackett, Alan; Wang, Guilin; Hon, Lawrence S; Fang, Gang; Swenberg, James A; Xiao, Andrew Z

Published In Nature, (2016 Apr 21)

Abstract: 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.

PubMed ID: 27027282 Exiting the NIEHS site

MeSH Terms: Adenine/analogs & derivatives*; Adenine/metabolism; AlkB Homolog 1, Histone H2a Dioxygenase; Animals; Cell Differentiation/genetics; DNA Methylation*; 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*; Evolution, Molecular; Gene Silencing; Long Interspersed Nucleotide Elements/genetics; Mammals/genetics; Mice; Mouse Embryonic Stem Cells/cytology; Mouse Embryonic Stem Cells/metabolism*; Up-Regulation/genetics; X Chromosome/genetics; X Chromosome/metabolism

Back
to Top