UMMS Affiliation

Department of Cell and Developmental Biology

Date

8-1-2011

Document Type

Article

Medical Subject Headings

Animals; Cell Differentiation; Chromatin; DNA; DNA Methylation; Embryo, Nonmammalian; Embryonic Development; Embryonic Stem Cells; Gene Expression Regulation, Developmental; Histones; Humans; Promoter Regions, Genetic; *Transcription, Genetic; Xenopus

Disciplines

Cell Biology | Developmental Biology | Molecular Biology | Molecular Genetics | Musculoskeletal Diseases | Nervous System Diseases

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.

Rights and Permissions

Citation: Genome Res. 2011 Aug;21(8):1313-27. doi: 10.1101/gr.114843.110. Epub 2011 Jun 2. Link to article on publisher's site

Comments

Publisher PDF posted as allowed by the publisher's license to publish at http://genome.cshlp.org/site/misc/GR_LicenseToPublish_2014_v4.pdf.

At the time of publication, Peter Jones was not yet affiliated with the University of Massachusetts Medical School.

Related Resources

Link to Article in PubMed

PubMed ID

21636662

Creative Commons License

Creative Commons Attribution-Noncommercial 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License

 
 

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