在细胞分化过程中,DNA可访问性和转录因子占用率对增强酶活性的贡献
Trevor Long1, Tapas Bhattacharyya1, Andrea Repele1
1Department of Biology, University of North Dakota, Grand Forks, ND 58202-9019, USA.
G3 (Bethesda, Md.)
|December 21, 2023
概括
转录因子 (TF) 结合,而不仅仅是DNA可访问性,在细胞分化过程中驱动基因表达. 特定部位的TF结合对于激活增强剂和调节基因活性至关重要.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- DNA可访问性影响转录因子 (TF) 结合和基因调节.
- 对于大多数基因来说,调节事件的精确序列,特别是DNA可访问性和TF结合之间的相互作用,仍然不清楚.
研究的目的:
- 研究结合点分辨率的DNA可访问性和巨细胞-中性粒细胞分化过程中的增强剂活性之间的动态关系.
- 确定驱动基因表达变化的致病性调节事件.
主要方法:
- 使用了高覆盖率的ATAC-Seq (使用测序测定转化酶可访问染色体) 数据.
- 采用特定站点的敲进记者基因来监测增强剂活性.
- 分析时间序列表达式数据.
主要成果:
- 增强剂活性在分化早期增加,在DNA总体可访问性显著增加之前.
- 峰值DNA可访问性发生在分化晚期,而没有相应的增强剂活性增加.
- 增加TF结合部位的可访问性与早期增强剂激活相关,表明TF结合驱动早期基因表达.
结论:
- 特定的转录因子结合,而不是一般的DNA可访问性,是提高基因表达的必要条件.
- 高分辨率的ATAC-Seq和时间序列表达数据可以阐明监管事件的顺序.
- 增强剂特异性TF结合是基因分化过程中基因表达动态的关键决定因素.
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