| First Author | Wu TP | Year | 2016 |
| Journal | Nature | Volume | 532 |
| Issue | 7599 | Pages | 329-33 |
| PubMed ID | 27027282 | Mgi Jnum | J:276409 |
| Mgi Id | MGI:6316531 | Doi | 10.1038/nature17640 |
| Citation | Wu TP, et al. (2016) DNA methylation on N(6)-adenine in mammalian embryonic stem cells. Nature 532(7599):329-33 |
| abstractText | 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. |
