重复DNA甲基化是通过附着结合信号调节的
Lisa-Marie Brenner1, Florian Meyer1, Haiqian Yang2
1Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany.
Communications biology
|March 7, 2024
概括
细胞密度对重复元素的DNA甲基化产生影响,揭示了一条涉及E-cadherin的途径,该途径维持了上皮组织的平衡. 这一发现揭示了染色质调节和细胞对细胞的粘附.
科学领域:
- 细胞生物学 细胞生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
背景情况:
- 基因甲基化对于基因转录和异色素蛋白的形成至关重要,影响细胞环境相互作用.
- 调节DNA甲基化分布的细胞外信号,特别是在重复的元素中,仍然在很大程度上是未知的.
- 在活细胞中研究DNA甲基化面临着方法上的挑战,特别是对于丰富的重复元素.
研究的目的:
- 发现信号通路,将重复元素中的染色质修饰连接到表皮粘附结合完整性.
- 研究细胞密度如何影响活细胞中的DNA甲基化模式.
- 为了确定参与将细胞密度信号传递到细胞核的分子参与者.
主要方法:
- 开发和利用CRISPR/dCas9生物传感器,用于在人类α卫星重复时对活细胞中DNA甲基化的监测.
- 在流与低密度乳腺上皮细胞单层中对α卫星重复甲基化的比较分析.
- 综合性扰动实验,以确定关键的分子介质.
主要成果:
- 与低密度培养相比,在汇聚细胞单层中观察到减少α卫星重复甲基化和增加的转录活性.
- 连接到actin细胞骨的连接蛋白E-cadherin被确定为信号中继到核的中心调解器.
- 在缺乏E-cadherin和接触抑制的癌细胞中,已识别的途径受损.
结论:
- 一个新的信号通路将细胞密度,重复元素甲基化和上皮粘附结合完整性联系起来.
- 电子干在将细胞密度信息传递到细胞核中起着至关重要的作用,影响色素.
- 癌细胞中这种途径的失调表明它在维持上皮组织恒常性方面的重要性.
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