Mouse/human sequence divergence in a region with a paternal-specific methylation imprint at the human H19 locus

Jinno, Yoshihiro; Sengoku, Kazuo; Nakao, Mitsuyoshi; Tamate, Kenichi; Miyamoto, Toshinobu; Matsuzaka, Tetsuo; Sutcliffe, James S.; Anan, Tadashi; Takuma, Naoyuki; Nishiwaki, Kunihiko; Ikeda, Yuichiro; Ishimaru, Tadayuki; Ishikawa, Mutsuo; Niikawa, Norio

doi:10.1093/hmg/5.8.1155

Cited by 87 publications

(62 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3). This was consistent with previous analyses of H19 methylation in human somatic cells (Zhang et al 1993;Jinno et al 1996). These results indicated that the appropriate imprinting status of human H19 was maintained in these mouse somatic cell hybrids.…”

Section: Maintenance Of the Imprinting Status Of Human H19 In Mouse Ssupporting

confidence: 93%

Epigenetic reprogramming of the human H19 gene in mouse embryonic cells does not erase the primary parental imprint

et al. 1998

View full text Add to dashboard Cite

show abstract

Section: Maintenance Of the Imprinting Status Of Human H19 In Mouse Ssupporting

confidence: 93%

Epigenetic reprogramming of the human H19 gene in mouse embryonic cells does not erase the primary parental imprint

et al. 1998

View full text Add to dashboard Cite

show abstract

“…1) and is normally maternally methylated (IGF2 DMR; ref. 28), whereas another is located upstream of H19 and is paternally methylated (29). The latter region harbors sequences known to bind to the zinc finger protein CTCF in a methylation-sensitive manner (18,30).…”

Section: Resultsmentioning

confidence: 99%

Frequent IGF2/H19 Domain Epigenetic Alterations and Elevated IGF2 Expression in Epithelial Ovarian Cancer

Murphy

Huang

Wen

et al. 2006

Molecular Cancer Research

125

103

View full text Add to dashboard Cite

Overexpression of the imprinted insulin-like growth factor-II (IGF2) is a prominent characteristic of gynecologic malignancies. The purpose of this study was to determine whether IGF2 loss of imprinting (LOI), aberrant H19 expression, and/or epigenetic deregulation of the IGF2/H19 imprinted domain contributes to elevated IGF2 expression in serous epithelial ovarian tumors. IGF2 LOI was observed in 5 of 23 informative serous epithelial ovarian cancers, but this did not correlate with elevated expression of IGF2 H19 RNA expression levels were also found not to correlate with IGF2 transcript levels. However, we identified positive correlations between elevated IGF2 expression and hypermethylation of CCCTC transcription factor binding sites 1 and 6 at the H19 proximal imprint center (P = 0.05 and 0.02, respectively). Hypermethylation of CCCTC transcription factor sites 1 and 6 was observed more frequently in cancer DNA compared with lymphocyte DNA obtained from women without malignancy (P < 0.0001 for both sites 1 and 6). Ovarian cancers were also more likely to exhibit maternal allele-specific hypomethylation upstream of the imprinted IGF2 promoters when compared with normal lymphocyte DNA (P = 0.004). This is the same region shown previously to be hypomethylated in colon cancers with IGF2 LOI, but this was not associated with LOI in ovarian cancers. Elevated IGF2 expression is a frequent event in serous ovarian cancer and this occurs in the absence of IGF2 LOI. These data indicate that the epigenetic changes observed in these cancers at the imprint center may contribute to IGF2 overexpression in a novel mechanistic manner. (Mol Cancer Res 2006;4(4):283 -92)

show abstract

“…To investigate whether there is abnormal methylation in the H19-DMR of HNSCC patients, we modified a protocol based on methylation-sensitive restriction enzyme PCR and posterior RFLP analysis, which permits allele differentiation (33). Using an AvaI RFLP, 91/95 cases were genotyped and 22 heterozygous informative cases were detected.…”

Section: Genomic Polymorphisms For Screening Of Informative Cases Andmentioning

confidence: 99%

H19-DMR allele-specific methylation analysis reveals epigenetic heterogeneity of CTCF binding site 6 but not of site 5 in head-and-neck carcinomas: A pilot case-control analysis

et al. 2006

View full text Add to dashboard Cite

Abstract. Aberrant methylation of seven potential binding sites of the CTCF factor in the differentially methylated region upstream of the H19 gene (H19-DMR) has been suggested as critical for the regulation of IGF2 and H19 imprinted genes. In this study, we analyzed the allele-specific methylation pattern of CTCF binding sites 5 and 6 using methylationsensitive restriction enzyme PCR followed by RFLP analysis in matched tumoral and lymphocyte DNA from head-andneck squamous cell carcinoma (HNSCC) patients, as well as in lymphocyte DNA from control individuals who were cancerfree. The monoallelic methylation pattern was maintained in CTCF binding site 5 in 22 heterozygous out of 91 samples analyzed. Nevertheless, a biallelic methylation pattern was detected in CTCF binding site 6 in a subgroup of HNSCC patients as a somatic acquired feature of tumor cells. An atypical biallelic methylation was also observed in both tumor and lymphocyte DNA from two patients, and at a high frequency in the control group (29 out of 64 informative controls). Additionally, we found that the C/T transition detected by HhaI RFLP suppressed one dinucleotide CpG in critical CTCF binding site 6, of a mutation showing polymorphic frequencies. Although a heterogeneous methylation pattern was observed after DNA sequencing modified by sodium bisulfite, the biallelic methylation pattern was confirmed in 9 out of 10 HNSCCs. These findings are likely to be relevant in the epigenetic regulation of the DMR, especially in pathological conditions in which the imprinting of IGF2 and H19 genes is disrupted.

show abstract

Mouse/human sequence divergence in a region with a paternal-specific methylation imprint at the human H19 locus

Cited by 87 publications

References 23 publications

Epigenetic reprogramming of the human H19 gene in mouse embryonic cells does not erase the primary parental imprint

Epigenetic reprogramming of the human H19 gene in mouse embryonic cells does not erase the primary parental imprint

Frequent IGF2/H19 Domain Epigenetic Alterations and Elevated IGF2 Expression in Epithelial Ovarian Cancer

H19-DMR allele-specific methylation analysis reveals epigenetic heterogeneity of CTCF binding site 6 but not of site 5 in head-and-neck carcinomas: A pilot case-control analysis

Contact Info

Product

Resources

About