Deep sequencing and de novo assembly of the mouse oocyte transcriptome define the contribution of transcription to the DNA methylation landscape.
Genome Biol
; 16: 209, 2015 Sep 25.
Article
em En
| MEDLINE
| ID: mdl-26408185
ABSTRACT
BACKGROUND:
Previously, a role was demonstrated for transcription in the acquisition of DNA methylation at imprinted control regions in oocytes. Definition of the oocyte DNA methylome by whole genome approaches revealed that the majority of methylated CpG islands are intragenic and gene bodies are hypermethylated. Yet, the mechanisms by which transcription regulates DNA methylation in oocytes remain unclear. Here, we systematically test the link between transcription and the methylome.RESULTS:
We perform deep RNA-Seq and de novo transcriptome assembly at different stages of mouse oogenesis. This reveals thousands of novel non-annotated genes, as well as alternative promoters, for approximately 10 % of reference genes expressed in oocytes. In addition, a large fraction of novel promoters coincide with MaLR and ERVK transposable elements. Integration with our transcriptome assembly reveals that transcription correlates accurately with DNA methylation and accounts for approximately 85-90 % of the methylome. We generate a mouse model in which transcription across the Zac1/Plagl1 locus is abrogated in oocytes, resulting in failure of DNA methylation establishment at all CpGs of this locus. ChIP analysis in oocytes reveals H3K4me2 enrichment at the Zac1 imprinted control region when transcription is ablated, establishing a connection between transcription and chromatin remodeling at CpG islands by histone demethylases.CONCLUSIONS:
By precisely defining the mouse oocyte transcriptome, this work not only highlights transcription as a cornerstone of DNA methylation establishment in female germ cells, but also provides an important resource for developmental biology research.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Oócitos
/
Metilação de DNA
/
Transcriptoma
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Genome Biol
Assunto da revista:
BIOLOGIA MOLECULAR
/
GENETICA
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Reino Unido