在MYEOV位点内进化保存的增强剂相关特征表明,这种非编码DNA区域在癌症中起着调控作用
Brigid S A Davidson1, Juliana Estefania Arcila-Galvis1, Marco Trevisan-Herraz1
1Biosciences Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.
Frontiers in cell and developmental biology
|August 14, 2024
概括
骨髓瘤过度表达基因 (MYEOV) 可能作为调节CCND1的增强剂,而不是原型瘤基因. 这种深度保存的增强元件.
科学领域:
- 基因组学就是基因组学.
- 分子生物学分子生物学
- 进化生物学 进化生物学
背景情况:
- 骨髓瘤过度表达 (MYEOV) 基因在各种癌症中显示出高水平的RNA,这表明原型瘤基因活性.
- 在灵长类动物中存在开放的读取框架 (ORF) 暗示了蛋白质编码潜力,但缺乏功能证据.
- 在癌症进展中MYEOV过度表达的作用仍然不清楚.
研究的目的:
- 调查MYEOV的功能作用,特别是其作为增强剂的潜力.
- 确定MYEOV是否调节其他基因,如CCND1和LTO1.
- 探索MYEOV及其监管元素的进化起源和保护.
主要方法:
- 对ATAC-STARR-seq数据的分析,以确认MYEOV.的增强剂活性.
- 在人体组织中检测增强体质素标记 (H3K4me1,H3K27ac).
- 3D基因组分析以确定色素相互作用.
- BLAST搜索和多序列对齐用于进化保护分析.
- 在小鼠中对同类区域进行比较分析,包括染色质状态和基因相互作用.
主要成果:
- MYEOV在人体B细胞中表现出增强剂活性,并与各种健康组织中的增强剂基因素标记有关.
- 3D基因组数据揭示了MYEOV 3'增强剂和CCND1基因之间的染色质相互作用.
- MYEOV增强剂序列在脊椎动物中保存,在CCND1正义体附近有一个哺乳动物保存的区域.
- 非人类灵长类动物,狗,老鼠和小鼠的同类区域显示保存的活性增强剂状态.
- 在小鼠中,MYEOV同源区域充当增强剂,与Ccnd1相互作用,类似于人类的相互作用.
结论:
- MYEOV是一种灵长类动物特有的基因,具有 *de novo* ORF,可能起源于一个进化古老的增强器区域.
- 这种保存的增强元件可以在人类和小鼠中调节CCND1.
- 这些发现表明,MYEOV的调节功能可以在非灵长类动物模型中研究,从而提供了对其在癌症中的作用的见解.
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