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How do you make a Cajal body or superenhancer and what do they have in common?

如何制作卡哈尔体或超级增强器？它们有什么共同点？

基本信息

批准号：
BB/W000172/1
负责人：
Stuart Wilson
金额：
$ 62.91万
依托单位：
University of Sheffield
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2022
资助国家：
英国
起止时间：
2022 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FW000172%2F1
关键词：
How do make Cajal body

项目摘要

Chromatin adopts a complex 3 dimensional shape in the mammalian nucleus which involves inter and intra-chromosomal contacts. How these contacts are made and enforced is not clear. When chromatin is isolated from cells, a large proportion of the material is RNA and proteins which associate with it. The role of this RNA remains largely uncharacterised, yet increasingly proteins which influence chromatin topology such as CTCF are being shown to associate with RNA. Therefore RNA is likely to play a key role in chromatin architecture and influence its activity. The Cajal body is an example of a region in the nucleus where intra chromosomal contacts occur, bringing together a specific collection of genes and the proteins which allow efficient transcription and processing of the RNA produced form those genes. A second example of chromatin contacts involves superenhancers which form loops with multiple target gene promoters, regulating their transcription. We have identified a protein which connects both Cajal body and superenhancer activities and binds RNA, chromatin and CTCF. We aim to test whether this protein forms part of an RNA:protein network which drives chromatin interactions in cells and ensures optimal transcription of target genes by recruitment of RNA polymerase II.

染色质在哺乳动物的细胞核中具有复杂的三维形状，它涉及到染色体间和染色体内的接触。目前尚不清楚这些联系是如何达成和执行的。当染色质从细胞中分离出来时，很大一部分物质是RNA和与之相关的蛋白质。这种RNA的作用在很大程度上仍未确定，但越来越多的影响染色质拓扑的蛋白质，如CTCF，被证明与RNA有关。因此，RNA很可能在染色质结构中发挥关键作用，并影响其活性。Cajal小体是细胞核中发生染色体内接触的区域的一个例子，它将一组特定的基因和蛋白质聚集在一起，使这些基因产生的RNA能够有效转录和处理。染色质接触的第二个例子涉及超级增强子，它与多个靶基因启动子形成环，调节它们的转录。我们已经鉴定出一种连接Cajal小体和超级增强子活性的蛋白质，并与RNA、染色质和CTCF结合。我们的目标是测试这种蛋白质是否形成RNA：蛋白质网络的一部分，该网络驱动细胞中的染色质相互作用，并通过招募RNA聚合酶II来确保目标基因的最佳转录。