全球双链DNA病毒的cis-regulatory景观
Tommy Henry Taslim1, Joseph Alexander Finkelberg2, Susan Kales3
1Molecular Biology, Cell Biology and Biochemistry Program, Boston University, Boston, MA 02215, USA.
bioRxiv : the preprint server for biology
|August 12, 2025
概括
研究人员在人类双链DNA (dsDNA) 病毒中绘制了超过2000个病毒的cis-regulatory元素 (CREs),揭示了它们的高密度和调节作用. 这为了解病毒基因表达和开发新的抗病毒策略提供了关键资源.
科学领域:
- 病毒学 病毒学
- 基因组学就是基因组学.
- 分子生物学分子生物学
背景情况:
- 双链DNA (dsDNA) 病毒依赖宿主转录机制进行基因表达.
- 病毒调节元件 (CREs) 和它们的转录因子 (TF) 相互作用对于病毒复制和免疫逃避至关重要.
- 大多数病毒CREs及其调节机制仍然未被描述.
研究的目的:
- 识别和功能性表征病毒CREs跨多种dSDNA病毒家族.
- 了解病毒基因表达的监管环境.
- 为病毒研究提供一个全面的资源.
主要方法:
- 大规模并行报告测试 (MPRA) 用于识别CREs.
- 和突变发生被用来探测TF结合和功能.
- 机器学习模型被开发用于预测病毒CRE调节器.
主要成果:
- 在27种dDNA病毒 (腺病毒,疹病毒,多种病毒,乳头瘤病毒家族) 中,大约确定了2000个CREs.
- 与人类基因组相比,病毒基因组具有更高的CRE密度.
- 病毒CREs经常重叠蛋白质编码序列,并具有促销器类特征.
- 确定了关键的病毒CRE调节器,包括SP,ETS,bZIP和信号激活的TF.
结论:
- 已经生成了感染人类的dsDNA病毒CREs的全面功能地图.
- 这张地图作为未来对病毒调节,活性化和进化的研究的基础.
- 这些发现对设计新型病毒载体和治疗策略有影响.
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