DNA hypomethylation at the ZNF206-exon 5 CpG island associated with             neuronal differentiation in mice and development of neuroblastoma in humans.
Differentiation of human neuroblastoma recapitulates neural crest development.             In our whole genome DNA methylation screening of tissue-specific differentially             methylated regions (T-DMRs) and developmental stage specific differentially methylated             regions (DS-DMRs) we reported that the exon 5 CpG island (CpGi) of Zfp206 (human:             ZNF206), which was required to maintain embryonic stem cells in a pluripotent             state, was one of potent brain and testis-specific T-DMRs in mice. In this study             methylation level of the CpG sites at Zfp206-exon 5 CpGi in mouse brain samples             at three different developmental stages (15-day-old embryo; E15, new born; NB,             12-week adult; AD) were quantitatively analyzed and it was identified that Zfp206-exon             5 CpGi was the DS-DMRs in mouse brain. In AD brains, Zfp206-exon 5 CpGi was significantly             hypomethylated and Zfp206 expression was repressed, compared with E15 and NB brains.             Hence, methylation level of human 5'-end of CpGi at ZNF206-exon 5, which is homologous             CpGi to mice, was analyzed in neuroblastomas. Although all four adrenal samples             showed complete methylation at the homologous region, we found the hypomethylation             in 7 out of 26 neuroblastomas and a significant association between the hypomethylation             and poor prognosis. In neuroblastoma cell lines and specimens, the hypomethylation             was also associated with ZNF206 expression. These data indicated that the changes             in DNA methylation levels at the Zfp206-exon 5 might be one of the important factors             during neuronal development in mice and that the hypomethylation of the homologous             region induced ZNF206 expression in humans and was associated with human neuroblastomagenesis.             Even though the function of ZNF206 and its expression regulation in neuroblastoma             remain elusive, ZNF206 might be a candidate differentiation suppressor and prognosis             marker in neuroblastoma.
Department of Pediatric Surgery, Nihon University School of Medicine,                     Tokyo, Japan.
Hiroyuki
H
Kawashima
Kiminobu
K
Sugito
Shinsuke
S
Yoshizawa
Shota
S
Uekusa
Takeshi
T
Furuya
Taro
T
Ikeda
Tsugumichi
T
Koshinaga
Yui
Y
Shinojima
Ryo
R
Hasegawa
Rajeev
R
Mishra
Jun
J
Igarashi
Makoto
M
Kimura
Xiaofei
X
Wang
Kyoko
K
Fujiwara
Srymoyee
S
Gosh
Hiroki
H
Nagase
D000311:Adrenal Glands / Q000737:chemistry / Q000502:physiology; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D018899:CpG Islands; D019175:DNA Methylation; D004268:DNA-Binding Proteins; D005091:Exons; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology; D009474:Neurons / Q000166:cytology*; D014157:Transcription Factors / Q000235:genetics*; D016335:Zinc Fingers / Q000235:genetics*
D004268:DNA-Binding Proteins; D014157:Transcription Factors; C514588:Zscan10 protein, mouse; C569380:ZSCAN10 protein, human