Sequence and functional comparison in the Beckwith-Wiedemann region:: implications for a novel imprinting centre and extended imprinting
Sequence and functional comparison in the Beckwith-Wiedemann region:: implications for a novel imprinting centre and extended imprinting
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DOI：
10.1093/hmg/9.18.2691
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发表时间：
2000-11-01
影响因子：
3.5
通讯作者：
Walter, J
中科院分区：
文献类型：
--
作者：
Engemann, S;Strödicke, M;Walter, J
哺乳动物中大多数印记基因的聚集组织表明协调的遗传和表观遗传控制机制。人类和小鼠之间的比较将有助于通过识别结构和功能相似性来阐明这些机制。以前我们报道了在小鼠远端7号染色体上的印记簇的中心部分与人类染色体11p15.5上的同源Beckwith-Wiedemann综合征（BWS）基因簇的比较，这里我们集中于0.5Mb的相邻序列，包括与BWS有关的KCNQ 1/Kcnq 1和CDKN 1C/Cdkn 1c基因，以及压印簇的一个建议的边界区域上。与先前分析的中心区域一样，这部分簇显示出高度保守的基因排列和结构。在KCNQ 1/Kcnq 1基因的3'部分发现了最显著的相似性，大部分是非编码序列。保守区域包括最近鉴定的KCNQ 1 OT 1/Kcnq 1 ot 1反义转录物，侧翼是一个非常保守的LINE/Line元件簇和一个CpG岛，我们显示该CpG岛携带母系生殖系甲基化印记。这个区域很可能是BWS集群中拟议的第二个印记中心（IC 2）。我们还确定了几个新的基因内部和外部先前提出的印迹集群的边界。其中一个基因外的集群，Obph 1，是印记在小鼠胎盘表明，至少在胚胎外组织的印记集群延伸到一个更大的域。
The clustered organization of most imprinted genes in mammals suggests coordinated genetic and epigenetic control mechanisms. Comparisons between human and mouse will help in elucidating these mechanisms by identifying structural and functional similarities. Previously we reported on such a comparison in the central part of the mouse imprinting cluster on distal chromosome 7 with the homologous Beckwith-Wiedemann syndrome (BWS) gene cluster on human chromosome 11p15.5, Here we focus on the adjacent sequences of 0.5 Mb including the KCNQ1/Kcnq1 and CDKN1C/Cdkn1c genes, which are implicated in BWS, and on one of the proposed boundary regions of the imprinting cluster. As in the previously analysed central region, this part of the cluster exhibits a highly conserved arrangement and structure of genes. The most striking similarity is found in the 3' part of the KCNQ1/Kcnq1 genes in large stretches of mostly non-coding sequences. The conserved region includes the recently identified KCNQ1OT1/Kcnq1ot1 antisense transcripts, flanked by a strikingly conserved cluster of LINE/Line elements and a CpG island which we show to carry a maternal germline methylation imprint. This region is likely to be the proposed second imprinting centre (IC2) in the BWS cluster. We also identified several novel genes inside and outside the previously proposed boundaries of the imprinting cluster. One of the genes outside the cluster, Obph1, is imprinted in mouse placenta indicating that at least in extra-embryonic tissues the imprinting cluster extends into a larger domain.