NDLI: Temporal uncoupling of the DNA methylome and transcriptional repression during embryogenesis

Content Provider	PubMed Central
Author	Bogdanović, Ozren Long, Steven W. Heeringen, Simon J. Van Brinkman, Arie B. Luis, Gómez-skarmeta Jose Stunnenberg, Hendrik G. Jones, Peter L. Veenstra, Gert Jan C.
Copyright Year	2011
Abstract	DNA methylation is a tightly regulated epigenetic mark associated with transcriptional repression. Next-generation sequencing of purified methylated DNA obtained from early Xenopus tropicalis embryos demonstrates that this genome is heavily methylated during blastula and gastrula stages. Although DNA methylation is largely absent from transcriptional start sites marked with histone H3 lysine 4 trimethylation (H3K4me3), we find both promoters and gene bodies of active genes robustly methylated. In contrast, DNA methylation is absent in large H3K27me3 domains, indicating that these two repression pathways have different roles. Comparison with chromatin state maps of human ES cells reveals strong conservation of epigenetic makeup and gene regulation between the two systems. Strikingly, genes that are highly expressed in pluripotent cells and in Xenopus embryos but not in differentiated cells exhibit relatively high DNA methylation. Therefore, we tested the repressive potential of DNA methylation using transient and transgenic approaches and show that methylated promoters are robustly transcribed in blastula- and gastrula-stage embryos, but not in oocytes or late embryos. These findings have implications for reprogramming and the epigenetic regulation of pluripotency and differentiation and suggest a relatively open, pliable chromatin state in early embryos followed by reestablished methylation-dependent transcriptional repression during organogenesis and differentiation.
Related Links	http://dx.doi.org/10.1101/gr.114843.110
Ending Page	1327
Page Count	15
Starting Page	1313
File Format	PDF
ISSN	10889051
e-ISSN	15495469
Journal	Genome Research
Issue Number	8
Volume Number	21
Language	English
Publisher	Cold Spring Harbor Laboratory Press
Publisher Date	2011-08-01
Access Restriction	Open
Rights Holder	Cold Spring Harbor Laboratory Press
Subject Keyword	Genetics(clinical) Genetics Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Genetics Genetics (clinical)

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