Sasaki H, Shimozaki K, Zubair M, Aoki N, Ohta K, Hatano N, Moore T, Feil R, Constancia M, Reik W, Rotwein P
Division of Disease Genes, Kyushu University, Fukuoka, Japan.
DNA Res. 1996 Oct 31;3(5):331-5. doi: 10.1093/dnares/3.5.331.
The mouse insulin-like growth factor II gene (Igf2) is physically linked to the insulin II gene (Ins2) and both are subject to tissue-specific genomic imprinting. The paternal-specific expression of Igf2 has been associated with hypermethylation of some CpG sites in the 5' flanking region and in the body of the gene. As a first step in analyzing the structural features of this imprinted locus, we here report the complete nucleotide sequence of Igf2, including all introns and the intergenic region adjacent to Ins2. This 28-kb segment of mouse chromosome 7 exhibits 80% overall identity with the corresponding rat sequence and has a high GC content of 52%. In addition to the known CpG island within the second Igf2 promoter, another island was identified approximately 2 kb 5' to the first exon. Other features of this locus include a 35-fold tandem repeat of an 11-bp sequence that overlaps Igf2 pseudo-exon 2, and a B2 repeat element in the intergenic region between Ins2 and Igf2. The GC-richness and the presence of CpG islands associated with tandem repeats are common features of imprinted genes and thus may play a role in the imprinting mechanism.
小鼠胰岛素样生长因子II基因(Igf2)与胰岛素II基因(Ins2)在物理上相连,且二者均受到组织特异性的基因组印记调控。Igf2的父本特异性表达与该基因5'侧翼区域及基因主体中某些CpG位点的高甲基化有关。作为分析该印记基因座结构特征的第一步,我们在此报告Igf2的完整核苷酸序列,包括所有内含子以及与Ins2相邻的基因间区域。小鼠7号染色体上的这个28 kb片段与相应的大鼠序列整体一致性达80%,且GC含量高达52%。除了第二个Igf2启动子内已知的CpG岛外,在第一个外显子上游约2 kb处还鉴定出另一个岛。该基因座的其他特征包括一个与Igf2假外显子2重叠的11 bp序列的35倍串联重复,以及Ins2和Igf2之间基因间区域的一个B2重复元件。富含GC以及存在与串联重复相关的CpG岛是印记基因的共同特征,因此可能在印记机制中发挥作用。