Genome-wide analysis of DNA methylation status of CpG islands in embryoid bodies, teratomas, and fetuses

Kremenskoy, Maksym; Kremenska, Yuliya; Ohgane, Jun; Hattori, Naka; Tanaka, Satoshi; Hashizume, Kazuyoshi; Shiota, Kunio

doi:10.1016/j.bbrc.2003.10.078

Cited by 57 publications

(50 citation statements)

References 34 publications

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“…DNA methylation, an epigenetic modification in CpG islands, results in transcriptional silencing of the genes that can alter genomic imprinting (12), chromatin structure modulation (13), development (14), somatic X-chromosome inactivation, and suppression of transposable elements (15). The 5-methylcytosine content of DNA markedly decreases in aging normal diploid fibroblasts, whereas methylation of DNA is stable in immortal cells (16).…”

Section: Introductionmentioning

confidence: 99%

Interferon Regulatory Factors IRF5 and IRF7 Inhibit Growth and Induce Senescence in Immortal Li-Fraumeni Fibroblasts

Tang

Roberts³

et al. 2008

Molecular Cancer Research

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Cellular immortalization is one of the prerequisite steps in carcinogenesis. By gene expression profiling, we have found that genes in the interferon (IFN) pathway were dysregulated during the spontaneous cellular immortalization of fibroblasts from Li-Fraumeni syndrome (LFS) patients with germ-line mutations in p53. IFN signaling pathway genes were down-regulated by epigenetic silencing during immortalization, and some of these same IFN-regulated genes were activated during replicative senescence. Bisulfite sequencing of the promoter regions of two IFN regulatory transcription factors (IRF5 and IRF7) revealed that IRF7, but not IRF5, was epigenetically silenced by methylation of CpG islands in immortal LFS cells. The induction of IRF7 gene by IFNA in immortal LFS cells was potentiated by pretreatment with the demethylation agent 5-aza-2 ¶-deoxycytidine. Overexpression of IRF5 and IRF7 revealed that they can act either alone or in tandem to activate other IFN-regulated genes. In addition, they serve to inhibit the proliferation rate and induce a senescence-related phenotype in immortal LFS cells. Furthermore, polyinosinic:polycytidylic acid treatment of the IRF-overexpressing cells showed a more rapid induction of several IFN-regulated genes. We conclude that the epigenetic inactivation of the IFN pathway plays a critical role in cellular immortalization, and the reactivation of IFN-regulated genes by transcription factors IRF5 and/or IRF7 is sufficient to induce cellular senescence. The IFN pathway may provide valuable molecular targets for therapeutic interventions at early stages of cancer development. (Mol Cancer Res 2008;6(5):770 -84)

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Section: Introductionmentioning

confidence: 99%

Interferon Regulatory Factors IRF5 and IRF7 Inhibit Growth and Induce Senescence in Immortal Li-Fraumeni Fibroblasts

Tang

Roberts³

et al. 2008

Molecular Cancer Research

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“…Both DNA methylation and demethylation occur during development (Kremenskoy et al 2003). However, it is unclear which is important in differentiation.…”

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confidence: 99%

Genome-wide demethylation during neural differentiation of P19 embryonal carcinoma cells

et al. 2008

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“…Various techniques have been utilized to obtain DNA methylation profiles of unique sequences, including: restriction land mark genomic scanning (RLGS) , genome-wide bisulfite sequencing (Eckhardt el al., 2006), and microarrays in combination with DNA methylation-sensitive restriction enzyme (Khulan et al, 2005;Yagi et al, 2008) or antibodies against 5-MeC (Weber et al, 2005). All of these studies have reported a substantial amount of T-DMRs by comparing DNA methylation profiles of various somatic tissues Kremenskoy et al, 2003;Song et al, 2005;Khulan et al, 2006;Eckhardt et al, 2006;Sakamoto et al, 2008;Yagi et al, 2008), stem cells Kremenskoy et al, 2003), germ cells Oakes et al, 2007;Weber et al, 2007), primary cell types (Weber et al, 2005;Eckhardt et al, 2006;Weber et al, 2007), and cells of different sex or ages (Weber et al, 2005;Eckhardt et al, 2006). For example, RLGS with Not I, a methylation-sensitive restriction enzyme, was used to analyze the genome-wide DNA methylation status (~1,500 loci) in mouse embryonic stem (ES) cells, embryonic germ (EG) cells, trophoblast stem (TS) cells, germ cells and several somatic tissues, which identified 247 T-DMRs where the methylation status is dependent on the cell or tissue type .…”

Section: Dna Methylation Profiles Of T-dmrs In Normal Cells and Tissuesmentioning

confidence: 99%

Interplay between DNA methylation, histone modification and chromatin remodeling in stem cells and during development

Ikegami¹,

Ohgane²,

Tanaka³

et al. 2009

Int. J. Dev. Biol.

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106

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Genes constitute only a small proportion of the mammalian genome, the majority of which is composed of non-genic repetitive elements including interspersed repeats and satellites. A unique feature of the mammalian genome is that there are numerous tissue-dependent, differentially methylated regions (T-DMRs) in the non-repetitive sequences, which include genes and their regulatory elements. The epigenetic status of T-DMRs varies from that of repetitive elements and constitutes the DNA methylation profile genome-wide. Since the DNA methylation profile is specific to each cell and tissue type, much like a fingerprint, it can be used as a means of identification. The formation of DNA methylation profiles is the basis for cell differentiation and development in mammals. The epigenetic status of each T-DMR is regulated by the interplay between DNA methyltransferases, histone modification enzymes, histone subtypes, non-histone nuclear proteins and non-coding RNAs. In this review, we will discuss how these epigenetic factors cooperate to establish cell-and tissue-specific DNA methylation profiles. KEY WORDS: epigenetics, DNA methylation, T-DMR, histone modification, chromatin remodeling Epigenetic systems in mammalian developmentIn unicellular organisms, each individual cell uses almost all of the genomic information and displays an essentially identical phenotype. In contrast, in mammals there are at least a few hundred different cell types based on a variety of physiological and morphological criteria. All of these cell types are derived from a single fertilized egg. The differentiation of each cell type is achieved without changes in DNA sequence, but through the coordinated utilization of subsets of genes. In order to achieve the proper temporal and spatial regulation of these genes throughout development, a set of epigenetic mechanisms are employed, which includes histone modifications and DNA methylation (Shiota, 2004;Lieb et al., 2006).In mammals, DNA methylation occurs through DNA methyltransferases (Dnmts) that operate within 5'-CG-3' dinucleInt.

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Genome-wide analysis of DNA methylation status of CpG islands in embryoid bodies, teratomas, and fetuses

Cited by 57 publications

References 34 publications

Interferon Regulatory Factors IRF5 and IRF7 Inhibit Growth and Induce Senescence in Immortal Li-Fraumeni Fibroblasts

Interferon Regulatory Factors IRF5 and IRF7 Inhibit Growth and Induce Senescence in Immortal Li-Fraumeni Fibroblasts

Genome-wide demethylation during neural differentiation of P19 embryonal carcinoma cells

Interplay between DNA methylation, histone modification and chromatin remodeling in stem cells and during development

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