Comparative sequence analysis of the imprinted Dlk1-Gtl2 locus in three mammalian species reveals highly conserved genomic elements and refines comparison with the Igf2-H19 region
Comparative sequence analysis of the imprinted Dlk1-Gtl2 locus in three mammalian species reveals highly conserved genomic elements and refines comparison with the Igf2-H19 region
复制标题
DOI：
10.1101/gr.206901
复制
发表时间：
2001-12-01
期刊：
影响因子：
7
通讯作者：
Ferguson-Smith, AC
中科院分区：
文献类型：
--
作者：
Paulsen, M;Takada, S;Ferguson-Smith, AC
小鼠12号染色体上的Dlk 1-Gtl 2结构域包含有可能有助于我们理解印记控制中涉及的共同特征的双印记基因。我们已经对小鼠和绵羊的这一保守区域进行了测序，并将人类序列纳入了三个物种的比较。该分析导致了精确的保守图和高度保守的序列元件的鉴定，其中一些我们先前已经显示在小鼠中差异甲基化。此外，该分析有助于鉴定位于Gt 12上游13-15 kb附近的富含CpG的串联重复序列。此外，我们已经确定了第三个印迹转录本，与最后一个Dlk 1外显子在小鼠中重叠。该转录本缺乏保守的开放阅读框，可能是通过切割延伸的Dlk 1转录本产生的。由于Dlk 1和Gtl 2共享许多特征明确的Igf 2-H19结构域的印迹特性，因此已经提出这两个区域可以以相同的方式调节。两个域的比较基因组检查表明，虽然有相似之处，其他功能是非常不同的，包括保守的CTCF结合位点的位置，和在监管区域的保护水平。
The Dlk1-Gtl2 domain on Mouse chromosome 12 contains reciprocally imprinted genes with the potential to contribute to our understanding of common features involved in imprinting control. We have sequenced this conserved region in the mouse and sheep and included the human sequence in a three species comparison. This analysis resulted in a precise conservation map and identification of highly conserved sequence elements, some of which we have shown previously to be differentially methylated in the mouse. Additionally, this analysis facilitated identification of a CpG-rich tandem repeat array located similar to 13-15 kb upstream of Gtl2. Furthermore, we have identified a third imprinted transcript that overlaps with the last Dlk1 exon in the Mouse. This transcript lacks a conserved open reading frame and is probably generated by cleavage of extended Dlk1 transcripts. Because Dlk1 and Gtl2 share many of the imprinting properties of the well-characterized Igf2-H19 domain, it has been proposed that the two regions may be regulated in the same way. Comparative genomic examination of the two domains indicates that although there are similarities, other features are very different, including the location of conserved CTCF-binding sites, and the level of conservation at regulatory regions.