一个模块化和可定制的CRISPR/Cas工具包用于Cis调节模块的表观基因组编辑
Lingrui Zhang1, Jianxin Fu2, Tiandan Long3
1Department of Horticulture and Landscape Architecture, Purdue University, West Lafayette, IN, 47907, USA.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|September 30, 2025
概括
新的表观基因组编辑工具,DNA脱甲基化 (dCd) 和DNA甲基化 (dCm),通过重编程cis调节元件 (CREs) 精确控制基因调节. 这些平台能够对表观遗传机制和合成生物学应用进行因果剖析.
科学领域:
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 合成生物学 合成生物学
背景情况:
- 基因调节由表观基因组和cis-regulome进行调节,包括cis调节元件 (CREs) 和模块 (CRMs).
- 通过表观遗传标记影响CRM功能的精确机制尚未完全理解.
- 针对性地操纵表观遗传标记对于剖析基因调节和工程细胞功能至关重要.
研究的目的:
- 开发和验证模块化表观基因组编辑框架,用于CRM活动的可编程剖析和工程.
- 为了研究DNA甲基化和CRM功能之间的因果关系.
- 探索这些工具在合成生物学和特征设计方面的潜力.
主要方法:
- 开发死Cas9合的DNA脱甲基化 (dCd) 和DNA甲基化 (dCm) 平台.
- 使用dCd调节植物中的甲基化水平和转录输出.
- 使用dCm系统在Saccharomyces cerevisiae中复制依赖甲基化的CRMs.
- 整合光遗传和温度敏感抑制剂用于可调节的调节.
主要成果:
- 该dCd系统可靠地调节CRM活动和共转录RNA处理,从而在植物中产生可预测的表型结果.
- 该dCm系统能够对酵母体的表观遗传调节进行因果剖析,证明了CRMs的跨物种可移植性.
- 发现了DNA甲基化和染色质修饰之间的交叉.
- 通过CRM工程实现了内源基因的逻辑控制和可调节,可逆调节.
结论:
- 模块化表观基因组编辑框架提供了一个多功能平台来解码和重编程cis-regulatory表观基因逻辑.
- 向DNA脱甲基和甲基化是理解和工程基因调节的可靠工具.
- 这些框架在特征设计和合成生物学中具有广泛的应用,为响应输入的合成表观基因组编辑器铺平了道路.
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