A novel sperm-specific hypomethylation sequence is a demethylation hotspot in human hepatocellular carcinomas

Nagai, Hisaki; Kim, Yong‐Sung; Yasuda, Takushi; Ohmachi, Yoshitaka; H, Yokouchi; Monden, Morito; Emi, Mitsuru; Konishi, Noboru; Nogami, Masahiro; Okumura, Katsuhiko; Matsubara, Kazuo

doi:10.1016/s0378-1119(99)00322-4

Cited by 33 publications

(21 citation statements)

References 16 publications

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“…42 It has also been shown that a 1.4-kb repetitive sequence was hypomethylated in sperm and HCC cells. 43 MS-RDA could also detect hypomethylated DNA regions in mouse HCC, which included the long interspersed nuclear element 1 (LINE-1) and ␣-enolase genes. 41 In addition to these methods, MCA/RDA also identified hypomethylated DNA regions as shown in the present study.…”

Section: Discussionmentioning

confidence: 99%

Aberrant expression of the MEL1S gene identified in association with hypomethylation in adult T-cell leukemia cells

Yoshida

Nosaka

Yasunaga

et al. 2004

Blood

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DNA methylation plays critical roles in the development and differentiation of mammalian cells, and its dysregulation has been implicated in oncogenesis. This study was designed to determine whether DNA hypomethylation-associated aberrant gene expression is involved in adult T-cell leukemia (ATL) leukemogenesis. We isolated hypomethylated DNA regions of ATL cells compared with peripheral blood mononuclear cells from a carrier by a methylated CpG-island amplification/representational difference analysis method. The DNA regions identified contained MEL1, CACNA1H, and Nogo receptor genes. Sequencing using sodium bisulfite-treated genomic DNAs revealed the decreased methylated CpG sites, confirming that this method detected hypomethylated DNA regions. Moreover, these hypomethylated genes were aberrantly transcribed. IntroductionAdult T-cell leukemia (ATL) is a neoplastic disease of CD4 ϩ T lymphocytes that is etiologically associated with human T-cell leukemia virus type I (HTLV-I). [1][2][3][4][5][6] After transmission, HTLV-I increases the number of infected cells through its viral proteins, including Tax. Tax encoded by the pX region between env and the 3Ј long terminal repeat (LTR) is an oncoprotein with pleiotropic actions, 7,8 including transactivation of the nuclear factor kappaB (NFB), serum responsive factor (SRF), and cyclic adenosine monophosphate (cAMP) response elementbinding protein (CREB) pathways; transrepression of genes, such as DNA polymerase ␤, lck, and p18 genes; and functional inactivation of p53, p16, and mitotic arrest-defective 1 (MAD1). 8,9 With these actions, Tax promotes the proliferation and inhibits apoptosis of infected cells, resulting in their clonal expansion and increased proviral load.The cumulative risk of developing ATL after HTLV-I infection was estimated to be 6% in men and 2% in women. 10 In addition, there is a long latent period before the onset of ATL, suggesting that additional factors other than viral proteins are implicated in leukemogenesis. Although somatic changes of genes, such as mutation of p53 11 or deletion of p16, 12 were reported in ATL, they were not so frequent in ATL cells and were predominantly observed in aggressive forms of ATL, such as acute and lymphoma types. This suggested that these genetic changes were implicated in the progression of ATL. In addition, it has been reported that DNA methylation of the p16 gene silenced its expression, indicating that epigenetic changes were also implicated in leukemogenesis. 13 Epigenetic changes include dysregulated DNA methylation in cancer cells, which consists of hypermethylation and hypomethylation of DNA. 14 Hypermethylation is frequently associated with gene silencing when hypermethylation occurs in the promoter region of genes. 15 The same mechanism is considered to regulate the transcriptional silencing of various tumor suppressor genes, including p16, 16 p15, 17 hMLH1, 18 BRCA1, 19 and GSTP1 genes. 20 From the perspective of the whole genome, genome-wide hypomethylation has been reported in cancer cells...

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Section: Discussionmentioning

confidence: 99%

Aberrant expression of the MEL1S gene identified in association with hypomethylation in adult T-cell leukemia cells

Yoshida

Nosaka

Yasunaga

et al. 2004

Blood

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“…Profiles of DNA methylation of T-DMRs using RLGS with NotI methyl-sensitive restriction enz ym e a s a la n d m ar k e n z ym e h a v e b e en produced for the mouse, rat, and human genomes [9,11,22]. These RLGS profiles represent the DNA methylation patterns of thousands of NotI sites that a r e m a i n l y l o c a t e d i n g e n i c r e g i o n s [ 2 3 ] .…”

Section: Analysis Of the Dna Methylation Profiles Of The Bovine Genomementioning

confidence: 99%

DNA Methylation Profiles of Donor Nuclei Cells and Tissues of Cloned Bovine Fetuses

Kremenskoy

Kremenska

Suzuki

et al. 2006

Journal of Reproduction and Development

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Abstract. Methylation of DNA in CpG islands plays an important role during fetal development and differentiation because CpG islands are preferentially located in upstream regions of mammalian genomic DNA, including the transcription start site of housekeeping genes and are also associated with tissue-specific genes. Somatic nuclear transfer (NT) technology has been used to generate live clones in numerous mammalian species, but only a low percentage of nuclear transferred animals develop to term. Abnormal epigenetic changes in the CpG islands of donor nuclei after nuclear transfer could contribute to a high rate of abortion during early gestation and increase perinatal death. These changes have yet to be explored. Thus, we investigated the genome-wide DNA methylation profiles of CpG islands in nuclei donor cells and NT animals. Using Restriction Landmark Genomic Scanning (RLGS), we showed, for the first time, the epigenetic profile formation of tissues from NT bovine fetuses produced from cumulus cells. From approximately 2600 unmethylated NotI sites visualized on the RLGS profile, at least 35 NotI sites showed different methylation statuses. Moreover, we proved that fetal and placental tissues from artificially inseminated and cloned cattle have tissuespecific differences in the genome-wide methylation profiles of the CpG islands. We also found that possible abnormalities occurred in the fetal brain and placental tissues of cloned animals.

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“…Similar types of repeats that are hypo-methylated has been observed in Wilms tumor, ovarian cancer and adenocarcinoma [1,75]. Additional types of tandem repeats are also involved in malignancies [7,15,31,36,[75][76][77]. Satellite DNA repeats sometimes show strongest DNA hypo-methylation for all type of sequence analyzed [15,56].…”

Section: Hypo-methylation Of Dna Repeats In Cancermentioning

confidence: 68%

“…This hypo-methylation has also been observed in non-tumor cells present adjacent to tumor cells [10,44,66,[79][80][81][82]. Repeat DNA hypo-methylation serves as highly informative marker [39, 75,83,84].…”

Section: Hypo-methylation Of Dna Repeats In Cancermentioning

confidence: 94%

“…LINE-1 is highly repeated gene sequence, hypo-methylation of LINE-1 and alu repeats have been observed in many types of cancer [70][71][72][73][74]. Similar types of repeats that are hypo-methylated has been observed in Wilms tumor, ovarian cancer and adenocarcinoma [1,75]. Additional types of tandem repeats are also involved in malignancies [7,15,31,36,[75][76][77].…”

Section: Hypo-methylation Of Dna Repeats In Cancermentioning

confidence: 99%

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DNA Methylation in Cancer Tissues

Asif¹,

Naveed²,

Rashid³

2017

J Cell Sci Ther

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Cancer linked DNA hypo-methylation and hyper-methylation are present throughout the human genome. The hyper-methylation facilitates cancer progress by repressing the tumor suppressor gene. Hypo-methylation contribution towards cancer has not yet been clear. Recent studies of tissue specific methylation have suggested that DNA hypo-methylation aid tumor formation by many pathways. Loss of DNA methylation associated with cancer may alter transcription. In addition, DNA hypo-methylation might affect promoter usage production of intra-genic non-coding RNA transcripts, co-transcriptional splicing and initiation and elongation of transcription. Studies of hemi methylation of DNA in cancerous cells as well as normal tissues suggest that active de-methylation can explain cancer associated DNA hypo-methylation. New studies that genomic 5-hydroxymethylcytosine is intermediate in DNA de-methylation exhibits cancer associated losses. It suggests that both decreased hydroxyl-methylation and methylation of DNA play important role in carcinogenesis.

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A novel sperm-specific hypomethylation sequence is a demethylation hotspot in human hepatocellular carcinomas

Cited by 33 publications

References 16 publications

Aberrant expression of the MEL1S gene identified in association with hypomethylation in adult T-cell leukemia cells

Aberrant expression of the MEL1S gene identified in association with hypomethylation in adult T-cell leukemia cells

DNA Methylation Profiles of Donor Nuclei Cells and Tissues of Cloned Bovine Fetuses

DNA Methylation in Cancer Tissues

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