Novel conserved elements upstream of the H19 gene are transcribed and act as mesodermal enhancers.

Novel conserved elements upstream of the H19 gene are transcribed and act as mesodermal enhancers.
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H19 基因上游的新保守元件被转录并充当中胚层增强子。

DOI:
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发表时间:
2002
期刊:
影响因子:
4.6
通讯作者:
M. Surani
M. Surani
中科院分区:
生物学2区
文献类型:
--
作者:
R. Drewell;Katharine L. Arney;T. Arima;S. Barton;J. Brenton;M. Surani

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相互印记的H19和Igf2基因在小鼠体内形成一个协调调控的130kb单位,由广泛分布的增强子、表观修饰的沉默因子和印记控制区(ICR)控制。人和小鼠基因组H19和Igf2的比较测序揭示了ICR上游两个新的同源性很高的区域,称为H19上游保守区(HUCS)。小鼠HUC1和HUC2作为有效的增强子,能够在一系列中胚层组织中驱动H19报告基因的表达。有趣的是,Huc序列在小鼠和人类中也是双等位转录的,但它们在13.5天胚胎的神经和内皮组织中的表达模式与它们的增强子功能不同。Huc中胚层增强剂位于ICR和H19的上游,以及它们与H19和Igf2的相互作用能力,需要对一系列中胚层组织中H19和Igf2印迹基因表达的顺式调节进行关键的重新评估。我们认为这些新的序列与H19上的ICR和Igf2差异甲基化区域1(DMR1)上受表观遗传调控的沉默分子相互作用。
The reciprocally imprinted H19 and Igf2 genes form a co-ordinately regulated 130 kb unit in the mouse controlled by widely dispersed enhancers, epigenetically modified silencers and an imprinting control region (ICR). Comparative human and mouse genomic sequencing between H19 and Igf2 revealed two novel regions of strong homology upstream of the ICR termed H19 upstream conserved regions (HUCs). Mouse HUC1 and HUC2 act as potent enhancers capable of driving expression of an H19 reporter gene in a range of mesodermal tissues. Intriguingly, the HUC sequences are also transcribed bi-allelically in mouse and human, but their expression pattern in neural and endodermal tissues in day 13.5 embryos is distinct from their enhancer function. The location of the HUC mesodermal enhancers upstream of the ICR and H19, and their capacity for interaction with both H19 and Igf2 requires critical re-evaluation of the cis-regulation of imprinted gene expression of H19 and Igf2 in a range of mesodermal tissues. We propose that these novel sequences interact with the ICR at H19 and the epigenetically regulated silencer at differentially methylated region 1 (DMR1) of Igf2.
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