独特的H3K9me3异染色体维护动态控制着不同的基因程序和重复在多能细胞中的重复
Jingchao Zhang1,2,3, Greg Donahue1,2,3, Michael B Gilbert2,4
1Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
bioRxiv : the preprint server for biology
|September 30, 2024
概括
基因组H3氨酸9三甲基化 (H3K9me3) heterochromatin 稳定性依赖于氨酸甲基转移酶 (KMTs) 和 HP1 蛋白. 这项研究揭示了明显的衰变速率和保护多能性的二元开关机制.
科学领域:
- 表观遗传学和基因调控
- 染色体生物学 染色体生物学
- 干细胞生物学 干细胞生物学
背景情况:
- 通过KMTs建立并通过HP1压缩的H3K9me3-heterochromatin抑制了血统基因和DNA重复.
- 了解H3K9me3-heterochromatin稳定性仅限于特定的域和重复.
研究的目的:
- 为了研究H3K9me3异染色素衰变和维护的动态.
- 确定控制异色染色素稳定性及其在多能性中的作用的因素.
主要方法:
- 工程 Suv39h2 淘汰赛小鼠胚胎干细胞,以快速消耗KMT.
- 分析了H3K9me3的衰变速率,染色体特征和转录因子结合模式.
- 研究HP1解离及其对染色质可访问性和多能性退出的影响.
主要成果:
- 无论是被动稀释还是积极去除,都会在12-24小时内导致H3K9me3的衰变.
- 在整个基因组中确定了四种不同的H3K9me3衰变速率,由染色质特征和转录因子结合预测.
- 在KMT耗尽时,HP1迅速分离,具有限制开拓因子结合和染色质开放的值,在12小时内影响多能性退出.
- 衰退的H3K9me3域揭示了剩余的HP1β峰值,这些峰值富含异染色素诱导蛋白质.
结论:
- 独特的H3K9me3-异染色体维护动态控制了基因网络和重复.
- 一个涉及HP1的二进制开关机制控制着异染色质的紧缩,染色质的可访问性和多能性.
- 这些发现揭示了对异染色素稳定性的新见解,以及它在保护多能性方面发挥的关键作用.
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