Analysis of CpG islands of trophoblast giant cells by restriction landmark genomic scanning

Ohgane, Jun; Aikawa, Jun Ichi; Ogura, Atsuo; Hattori, Naka; Ogawa, Tomoya; Shiota, Kunio

doi:10.1002/(sici)1520-6408(1998)22:2<132::aid-dvg3>3.0.co;2-7

Cited by 67 publications

(67 citation statements)

References 33 publications

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“…CpG islands (CGIs) have been identified as CpG-rich regions that are associated with ∼50% of the promoter regions in the mouse genome (Bird et al 1985;GardinerGarden and Frommer 1987). Previous genome-wide DNA methylation analyses, focusing on CGIs, have indicated that every cell and tissue type has a unique DNA methylation profile, comprising at least hundreds of T-DMRs (Ohgane et al 1998;Shiota et al 2002;Strichman-Almashanu et al 2002), and these data suggested that a methylation profile could be used to identify cell types (Shiota 2004).…”

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DNA methylation profile of tissue-dependent and differentially methylated regions (T-DMRs) in mouse promoter regions demonstrating tissue-specific gene expression

et al. 2008

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DNA methylation constitutes an important epigenetic regulation mechanism in many eukaryotes, although the extent of DNA methylation in the regulation of gene expression in the mammalian genome is poorly understood. We developed D-REAM, a genome-wide DNA methylation analysis method for tissue-dependent and differentially methylated region (T-DMR) profiling with restriction tag-mediated amplification in mouse tissues and cells. Using a mouse promoter tiling array covering a region from −6 to 2.5 kb (∼30,000 transcription start sites), we found that over 3000 T-DMRs are hypomethylated in liver compared to cerebrum. The DNA methylation profile of liver was distinct from that of kidney and spleen. This hypomethylation profile marked genes that are specifically expressed in liver, including key transcription factors such as Hnf1a and Hnf4a. Genes with T-DMRs, especially those lacking CpG islands and those with HNF-1A binding motifis in their promoters, showed good correlation between their tissue-specific expression and liver hypomethylation status. T-DMRs located downstream from their transcription start sites also showed tissue-specific gene expression. These data indicate that multilayered regulation of tissue-specific gene function could be elucidated by DNA methylation tissue profiling.

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DNA methylation profile of tissue-dependent and differentially methylated regions (T-DMRs) in mouse promoter regions demonstrating tissue-specific gene expression

et al. 2008

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“…It has been thought that most CpG islands remain unmethylated, even in cell types that do not express genes (Bird 2002). However, changes in DNA methylation linked to tissue-specific gene expression have been seen sporadically in CpG-rich promoters (Ohgane et al 1998;Song et al 2005).…”

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

et al. 2008

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“…Attempts to quantify DNA content by cytophotometry were consistent with integral genome doublings in some cells, but showed others with DNA values lower than multiples of 2C (15). A restriction landmark genomic scanning study of CpG islands in late gestation rat placental junctional zone tissue, which contains TGCs, indicated that nearly all of the ∼1,000 loci tested showed no differential replication (59). In situ hybridization signals with satellite DNA probes indicated replication of the heterochromatin in TGCs (18).…”

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Fundamental differences in endoreplication in mammals and Drosophila revealed by analysis of endocycling and endomitotic cells

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et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Throughout the plant and animal kingdoms specific cell types become polyploid, increasing their DNA content to attain a large cell size. In mammals, megakaryocytes (MKs) become polyploid before fragmenting into platelets. The mammalian trophoblast giant cells (TGCs) exploit their size to form a barrier between the maternal and embryonic tissues. The mechanism of polyploidization has been investigated extensively in Drosophila , in which a modified cell cycle—the endocycle, consisting solely of alternating S and gap phases—produces polyploid tissues. During S phase in the Drosophila endocycle, heterochromatin and specific euchromatic regions are underreplicated and reduced in copy number. Here we investigate the properties of polyploidization in murine MKs and TGCs. We induced differentiation of primary MKs and directly microdissected TGCs from embryonic day 9.5 implantation sites. The copy number across the genome was analyzed by array-based comparative genome hybridization. In striking contrast to Drosophila , the genome was uniformly and integrally duplicated in both MKs and TGCs. This was true even for heterochromatic regions analyzed by quantitative PCR. Underreplication of specific regions in polyploid cells is proposed to be due to a slower S phase, resulting from low expression of S-phase genes, causing failure to duplicate late replicating genomic intervals. We defined the transcriptome of TGCs and found robust expression of S-phase genes. Similarly, S-phase gene expression is not repressed in MKs, providing an explanation for the distinct endoreplication parameters compared with Drosophila . Consistent with TGCs endocycling rather than undergoing endomitosis, they have low expression of M-phase genes.

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Analysis of CpG islands of trophoblast giant cells by restriction landmark genomic scanning

Cited by 67 publications

References 33 publications

DNA methylation profile of tissue-dependent and differentially methylated regions (T-DMRs) in mouse promoter regions demonstrating tissue-specific gene expression

DNA methylation profile of tissue-dependent and differentially methylated regions (T-DMRs) in mouse promoter regions demonstrating tissue-specific gene expression

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

Fundamental differences in endoreplication in mammals and Drosophila revealed by analysis of endocycling and endomitotic cells

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