DNA methylation on N(6)-adenine in mammalian embryonic stem cells.
Nature
; 532(7599): 329-33, 2016 Apr 21.
Article
en En
| MEDLINE
| ID: mdl-27027282
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.
Texto completo:
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Bases de datos:
MEDLINE
Asunto principal:
Adenina
/
Metilación de ADN
/
Epigénesis Genética
/
Células Madre Embrionarias de Ratones
Límite:
Animals
Idioma:
En
Revista:
Nature
Año:
2016
Tipo del documento:
Article
País de afiliación:
Estados Unidos