希斯脱酶-1对于神经虫的表观基因组稳定性是必需的
Felicia Ebot-Ojong1, Aileen R Ferraro2, Rochelle E Yap2
1Department of Genetics, University of Georgia, Athens, GA 30602.
概括
基因组脱乙酶1 (HDA-1) 对于维持Neurospora crassa的表观基因组稳定性至关重要. 它的缺失导致染色质标记的渐进性衰变和基因抑制,突出显示HDA-1的存在.
科学领域:
- 在真核生物体中表观遗传学和染色质调节.
- 基因沉默和异色染色体形成的分子机制.
- 菌类生物学和表观基因组维护.
背景情况:
- 多组 (PcG) 蛋白质和多抑制复合体2 (PRC2) 通过像H3K27me3.3.这样的基因基因修饰稳定地抑制基因.
- 基因组脱乙酶 (HDACs) 与异染色素和PcG抑制的染色素有关,但它们的具体作用尚不清楚.
- 在Neurospora crassa中,H3K27me3沉积涉及ASH1和HP1,而低乙化是一个关键特征.
研究的目的:
- 为了确定抑制PRC2-甲基化基因所必需的HDACs.
- 阐明HISTONE DEACETYLASE-1 (HDA-1) 在H3K27me3模式和表观基因组稳定性中的作用.
- 研究HDA-1损失对表观基因组的长期后果.
主要方法:
- 基因查以确定基因抑制所需的HDACs.
- 在野生型和突变菌株中分析基因组修饰 (H3K27me3,H3K9me3) 和基因组乙化.
- 在实验室"衰老"实验中,在数百个核分区中构建了一个新的Dhdha-1菌株.
主要成果:
- HDA-1的丧失导致PRC2-甲基化基因的激活和H3K27me3.3的耗尽.
- 由于HDA-1缺乏,导致H3K9me3的减少,过乙化,以及H3K27me3 / H3K36me3在构成性异质染色素中的异常丰富.
- 染色域蛋白-2 (CDP-2) 是需要HDA-1向和正常的H3K27me3模式.
- 删除hda-1会导致随着时间的推移进步的表观基因组衰变.
结论:
- HDA-1对于维持H3K27me3模式和对PcG向基因的转录抑制至关重要.
- HDA-1在调节构成性异质染色素和防止异常基因组修饰方面发挥着关键作用.
- HDA-1是表观基因组稳定性的关键调节者,其损失导致Neurospora crassa的渐进性功能障碍.
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