UMMS Affiliation
Department of Cell and Developmental Biology
Publication Date
2011-08-01
Document Type
Article
Subjects
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
Publisher PDF posted as allowed by the publisher's license to publish at http://genome.cshlp.org/site/misc/GR_LicenseToPublish_2014_v4.pdf.
DOI of Published Version
10.1101/gr.114843.110
Source
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
Journal/Book/Conference Title
Genome research
Related Resources
PubMed ID
21636662
Repository Citation
Bogdanovic, Ozren; Long, Steven W.; van Heeringen, Simon J.; Brinkman, Arie B.; Gomez-Skarmeta, Jose Luis; Stunnenberg, Hendrik G.; Jones, Peter L.; and Veenstra, Gert Jan C., "Temporal uncoupling of the DNA methylome and transcriptional repression during embryogenesis" (2011). Peter Jones Lab Publications. 16.
https://escholarship.umassmed.edu/peterjones/16
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License
Included in
Cell Biology Commons, Developmental Biology Commons, Molecular Biology Commons, Molecular Genetics Commons, Musculoskeletal Diseases Commons, Nervous System Diseases Commons
Comments
At the time of publication, Peter Jones was not yet affiliated with the University of Massachusetts Medical School.