Shirohzu Hisao, Yokomine Takaaki, Sato Chiyoko, Kato Reiko, Toyoda Atsushi, Purbowasito Wahyu, Suda Chikako, Mukai Tsunehiro, Hattori Masahira, Okumura Katsuzumi, Sakaki Yoshiyuki, Sasaki Hiroyuki
Division of Human Genetics, Department of Integrated Genetics, National Institute of Genetics, Research Organization of Information and Systems, 1111 Yata, Mishima 411-8540, Japan.
DNA Res. 2004 Oct 31;11(5):325-34. doi: 10.1093/dnares/11.5.325.
Mammalian genes subject to genomic imprinting often form clusters and are regulated by long-range mechanisms. The distal imprinted domain of mouse chromosome 7 is orthologous to the Beckwith-Wiedemann syndrome domain in human chromosome 11p15.5 and contains at least 13 imprinted genes. This domain consists of two subdomains, which are respectively regulated by an imprinting center. We here report the finished-quality sequence of a 0.6-Mb region encompassing the more centromeric subdomain. The sequence contains four imprinted genes (Ascl2/Mash2, Ins2, Igf2 and H19) and reveals previously unidentified CpG islands and tandem repeats, which may be features of imprinted genes. Most interestingly, a unique 210-kb segment consisting almost exclusively of tandem repeats and retroelements is identified. This segment, located between Th and Ins2, has features of heterochromatin-forming DNA and is highly methylated at CpG sites. The segment exhibits asynchronous replication on the parental chromosomes, a feature of the imprinted domains. We propose that this repeat segment could serve either as a boundary between the two subdomains or as a target for epigenetic chromatin modifications that regulate imprinting.
经历基因组印记的哺乳动物基因通常形成基因簇,并受远程机制调控。小鼠7号染色体的远端印记区域与人类11号染色体p15.5上的贝克威思-维德曼综合征区域直系同源,且包含至少13个印记基因。该区域由两个亚区域组成,分别由一个印记中心调控。我们在此报告了一个包含更靠近着丝粒亚区域的0.6兆碱基区域的完成质量序列。该序列包含四个印记基因(Ascl2/Mash2、Ins2、Igf2和H19),并揭示了先前未识别的CpG岛和串联重复序列,这些可能是印记基因的特征。最有趣的是,鉴定出一个几乎完全由串联重复序列和逆转录元件组成的独特210千碱基片段。该片段位于Th和Ins2之间,具有形成异染色质的DNA特征,且在CpG位点高度甲基化。该片段在亲代染色体上表现出异步复制,这是印记区域的一个特征。我们提出,这个重复片段可能作为两个亚区域之间的边界,或者作为调控印记的表观遗传染色质修饰的靶点。