XB-ART-43338
Genome Res
2011 Aug 01;218:1313-27. doi: 10.1101/gr.114843.110.
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Temporal uncoupling of the DNA methylome and transcriptional repression during embryogenesis.
Bogdanovic O
,
Long SW
,
van Heeringen SJ
,
Brinkman AB
,
Gómez-Skarmeta JL
,
Stunnenberg HG
,
Jones PL
,
Veenstra GJ
.
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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.
???displayArticle.pubmedLink??? 21636662
???displayArticle.pmcLink??? PMC3149498
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???displayArticle.grants??? [+]
R01 HD054356 NICHD NIH HHS
???displayArticle.gses??? GSE23913: NCBI
References [+] :
Akkers,
A hierarchy of H3K4me3 and H3K27me3 acquisition in spatial gene regulation in Xenopus embryos.
2009, Pubmed,
Xenbase
Akkers, A hierarchy of H3K4me3 and H3K27me3 acquisition in spatial gene regulation in Xenopus embryos. 2009, Pubmed , Xenbase
Amir, Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. 1999, Pubmed
Azuara, Chromatin signatures of pluripotent cell lines. 2006, Pubmed
Bannister, Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain. 2001, Pubmed
Benson, Tandem repeats finder: a program to analyze DNA sequences. 1999, Pubmed
Bernstein, A bivalent chromatin structure marks key developmental genes in embryonic stem cells. 2006, Pubmed
Bird, CpG-rich islands and the function of DNA methylation. , Pubmed
Bird, DNA methylation patterns and epigenetic memory. 2002, Pubmed
Blankenberg, A framework for collaborative analysis of ENCODE data: making large-scale analyses biologist-friendly. 2007, Pubmed
Bock, Quantitative comparison of genome-wide DNA methylation mapping technologies. 2010, Pubmed
Bogdanović, DNA methylation and methyl-CpG binding proteins: developmental requirements and function. 2009, Pubmed , Xenbase
Boyer, Core transcriptional regulatory circuitry in human embryonic stem cells. 2005, Pubmed
Brinkman, Whole-genome DNA methylation profiling using MethylCap-seq. 2010, Pubmed
Carro, A novel protein, Xenopus p20, influences the stability of MeCP2 through direct interaction. 2004, Pubmed , Xenbase
Chahrour, MeCP2, a key contributor to neurological disease, activates and represses transcription. 2008, Pubmed
Chamberlain, Polycomb repressive complex 2 is dispensable for maintenance of embryonic stem cell pluripotency. 2008, Pubmed
Chen, Establishment and maintenance of genomic methylation patterns in mouse embryonic stem cells by Dnmt3a and Dnmt3b. 2003, Pubmed
Choi, Nucleosome deposition and DNA methylation at coding region boundaries. 2009, Pubmed
Cooper, Unmethylated domains in vertebrate DNA. 1983, Pubmed
Cross, Purification of CpG islands using a methylated DNA binding column. 1994, Pubmed
Czermin, Drosophila enhancer of Zeste/ESC complexes have a histone H3 methyltransferase activity that marks chromosomal Polycomb sites. 2002, Pubmed
Dunican, xDnmt1 regulates transcriptional silencing in pre-MBT Xenopus embryos independently of its catalytic function. 2008, Pubmed , Xenbase
Edgar, NCBI GEO standards and services for microarray data. 2006, Pubmed
Fouse, Promoter CpG methylation contributes to ES cell gene regulation in parallel with Oct4/Nanog, PcG complex, and histone H3 K4/K27 trimethylation. 2008, Pubmed
Fuks, The DNA methyltransferases associate with HP1 and the SUV39H1 histone methyltransferase. 2003, Pubmed
Gardiner-Garden, CpG islands in vertebrate genomes. 1987, Pubmed
Hashimshony, The role of DNA methylation in setting up chromatin structure during development. 2003, Pubmed
Hellsten, The genome of the Western clawed frog Xenopus tropicalis. 2010, Pubmed , Xenbase
Hendrich, Identification and characterization of a family of mammalian methyl-CpG binding proteins. 1998, Pubmed
Hendrich, The methyl-CpG binding domain and the evolving role of DNA methylation in animals. 2003, Pubmed
Hu, The N-terminus of histone H3 is required for de novo DNA methylation in chromatin. 2009, Pubmed
Iwano, Xenopus MBD3 plays a crucial role in an early stage of development. 2004, Pubmed , Xenbase
Jackson, Severe global DNA hypomethylation blocks differentiation and induces histone hyperacetylation in embryonic stem cells. 2004, Pubmed
Jackson-Grusby, Loss of genomic methylation causes p53-dependent apoptosis and epigenetic deregulation. 2001, Pubmed
Jair, De novo CpG island methylation in human cancer cells. 2006, Pubmed
Jones, Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. 1998, Pubmed , Xenbase
Jurka, Repetitive sequences in complex genomes: structure and evolution. 2007, Pubmed
Kaludov, MeCP2 driven transcriptional repression in vitro: selectivity for methylated DNA, action at a distance and contacts with the basal transcription machinery. 2000, Pubmed
Kangaspeska, Transient cyclical methylation of promoter DNA. 2008, Pubmed
Kass, DNA methylation directs a time-dependent repression of transcription initiation. 1997, Pubmed , Xenbase
Kay, The 1723 element: a long, homogeneous, highly repeated DNA unit interspersed in the genome of Xenopus laevis. 1983, Pubmed , Xenbase
Kay, Transcription of a long, interspersed, highly repeated DNA element in Xenopus laevis. 1984, Pubmed , Xenbase
Kent, The human genome browser at UCSC. 2002, Pubmed
Komashko, Using ChIP-chip technology to reveal common principles of transcriptional repression in normal and cancer cells. 2008, Pubmed
Kondo, Gene silencing in cancer by histone H3 lysine 27 trimethylation independent of promoter DNA methylation. 2008, Pubmed
Kroll, Transgenic Xenopus embryos from sperm nuclear transplantations reveal FGF signaling requirements during gastrulation. 1996, Pubmed , Xenbase
Landeira, Jarid2 is a PRC2 component in embryonic stem cells required for multi-lineage differentiation and recruitment of PRC1 and RNA Polymerase II to developmental regulators. 2010, Pubmed
Landsberger, The heat shock response in Xenopus oocytes, embryos, and somatic cells: a regulatory role for chromatin. 1995, Pubmed , Xenbase
Laurent, Dynamic changes in the human methylome during differentiation. 2010, Pubmed
Lee, Control of developmental regulators by Polycomb in human embryonic stem cells. 2006, Pubmed
Leeb, Ring1B is crucial for the regulation of developmental control genes and PRC1 proteins but not X inactivation in embryonic cells. 2007, Pubmed
Leeb, Polycomb complexes act redundantly to repress genomic repeats and genes. 2010, Pubmed
Li, Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. 1992, Pubmed
Li, Mapping short DNA sequencing reads and calling variants using mapping quality scores. 2008, Pubmed
Lindroth, Dual histone H3 methylation marks at lysines 9 and 27 required for interaction with CHROMOMETHYLASE3. 2004, Pubmed
Lister, Human DNA methylomes at base resolution show widespread epigenomic differences. 2009, Pubmed
Marini, Differential compartmentalization of plasmid DNA microinjected into Xenopus laevis embryos relates to replication efficiency. 1991, Pubmed , Xenbase
Martens, PML-RARalpha/RXR Alters the Epigenetic Landscape in Acute Promyelocytic Leukemia. 2010, Pubmed
Mayer, Demethylation of the zygotic paternal genome. 2000, Pubmed
Meissner, Genome-scale DNA methylation maps of pluripotent and differentiated cells. 2008, Pubmed
Mikkelsen, Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. 2007, Pubmed
Mohn, Methylated DNA immunoprecipitation (MeDIP). 2009, Pubmed
Mohn, Lineage-specific polycomb targets and de novo DNA methylation define restriction and potential of neuronal progenitors. 2008, Pubmed
Müller, Histone methyltransferase activity of a Drosophila Polycomb group repressor complex. 2002, Pubmed
Nan, Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. 1998, Pubmed
Newport, A major developmental transition in early Xenopus embryos: II. Control of the onset of transcription. 1982, Pubmed , Xenbase
Newport, A major developmental transition in early Xenopus embryos: I. characterization and timing of cellular changes at the midblastula stage. 1982, Pubmed , Xenbase
Okano, DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. 1999, Pubmed
Ooi, DNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA. 2007, Pubmed
Oswald, Active demethylation of the paternal genome in the mouse zygote. 2000, Pubmed
Ramsahoye, Non-CpG methylation is prevalent in embryonic stem cells and may be mediated by DNA methyltransferase 3a. 2000, Pubmed
Rush, Targeting of EZH2 to a defined genomic site is sufficient for recruitment of Dnmt3a but not de novo DNA methylation. 2009, Pubmed
Santos-Rosa, Active genes are tri-methylated at K4 of histone H3. 2002, Pubmed
Schulz, Methylation of endogenous human retroelements in health and disease. 2006, Pubmed
Selker, Genome defense and DNA methylation in Neurospora. 2004, Pubmed
Serre, MBD-isolated Genome Sequencing provides a high-throughput and comprehensive survey of DNA methylation in the human genome. 2010, Pubmed
Shahbazian, Molecular genetics of Rett syndrome and clinical spectrum of MECP2 mutations. 2001, Pubmed
Stancheva, DNA methylation at promoter regions regulates the timing of gene activation in Xenopus laevis embryos. 2002, Pubmed , Xenbase
Stancheva, Loss of the maintenance methyltransferase, xDnmt1, induces apoptosis in Xenopus embryos. 2001, Pubmed , Xenbase
Stancheva, A mutant form of MeCP2 protein associated with human Rett syndrome cannot be displaced from methylated DNA by notch in Xenopus embryos. 2003, Pubmed , Xenbase
Stancheva, Transient depletion of xDnmt1 leads to premature gene activation in Xenopus embryos. 2000, Pubmed , Xenbase
Stock, Ring1-mediated ubiquitination of H2A restrains poised RNA polymerase II at bivalent genes in mouse ES cells. 2007, Pubmed
Takai, Comprehensive analysis of CpG islands in human chromosomes 21 and 22. 2002, Pubmed
Tanay, Hyperconserved CpG domains underlie Polycomb-binding sites. 2007, Pubmed
Taylor, Using galaxy to perform large-scale interactive data analyses. 2007, Pubmed
Thomson, CpG islands influence chromatin structure via the CpG-binding protein Cfp1. 2010, Pubmed
Tsumura, Maintenance of self-renewal ability of mouse embryonic stem cells in the absence of DNA methyltransferases Dnmt1, Dnmt3a and Dnmt3b. 2006, Pubmed
van Heeringen, Nucleotide composition-linked divergence of vertebrate core promoter architecture. 2011, Pubmed , Xenbase
Veenstra, Constitutive genomic methylation during embryonic development of Xenopus. 2001, Pubmed , Xenbase
Veenstra, Translation of maternal TATA-binding protein mRNA potentiates basal but not activated transcription in Xenopus embryos at the midblastula transition. 1999, Pubmed , Xenbase
Vermeulen, Selective anchoring of TFIID to nucleosomes by trimethylation of histone H3 lysine 4. 2007, Pubmed
Viré, The Polycomb group protein EZH2 directly controls DNA methylation. 2006, Pubmed
Wade, Mi-2 complex couples DNA methylation to chromatin remodelling and histone deacetylation. 1999, Pubmed , Xenbase
Weber, Chromosome-wide and promoter-specific analyses identify sites of differential DNA methylation in normal and transformed human cells. 2005, Pubmed
Weber, Genomic patterns of DNA methylation: targets and function of an epigenetic mark. 2007, Pubmed
Wysocka, WDR5 associates with histone H3 methylated at K4 and is essential for H3 K4 methylation and vertebrate development. 2005, Pubmed , Xenbase
Yamada, Spatiotemporal, allelic, and enforced expression of Ximpact, the Xenopus homolog of mouse imprinted gene impact. 1999, Pubmed , Xenbase
Zhang, Model-based analysis of ChIP-Seq (MACS). 2008, Pubmed
Zhang, Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation. 1999, Pubmed
Zilberman, Genome-wide analysis of Arabidopsis thaliana DNA methylation uncovers an interdependence between methylation and transcription. 2007, Pubmed