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？

• 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

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.

染色质在哺乳动物核中采用复杂的3维形状，涉及间和染色体内接触。这些联系方式的建立和执行尚不清楚。当从细胞中分离染色质时，很大一部分材料是RNA和与之相关的蛋白质。该RNA的作用在很大程度上没有表征，但越来越多的蛋白质影响了诸如CTCF之类的染色质拓扑，也证明与RNA相关。因此，RNA可能在染色质体系结构中起关键作用并影响其活性。 Cajal体是核内染色体接触的核中区域的一个例子，将特定的基因集合和蛋白质集合在一起，这些蛋白质允许有效地转录和加工RNA产生的RNA形成这些基因。染色质接触的第二个示例涉及超级角色，这些超级角色用多个靶基因启动子形成循环，从而调节其转录。我们已经确定了一种连接Cajal体和超级角色活性并结合RNA，染色质和CTCF的蛋白质。我们旨在测试该蛋白是否构成RNA的一部分：蛋白质网络，该蛋白网络驱动细胞中的染色质相互作用并确保通过募集RNA聚合酶II的最佳转录。