通过异染色素原体的表观基因沉默
Sito Torres-Garcia1, Imtiyaz Yaseen1, Manu Shukla1
1Wellcome Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, UK.
Nature
|September 10, 2020
概括
裂变酵母通过表观遗传变化产生咖啡因耐药性,特别是素H3素9甲基化 (H3K9me) 异染色体,使其能够在没有遗传突变的情况下适应. 这种表观遗传机制为生存提供了一种投注策略.
科学领域:
- 表观遗传学和基因调控
- 微生物遗传学
- 染色体生物学
背景情况:
- 基因组H3氨酸9甲基化 (H3K9me) 形成异染色素,使基因沉默.
- 在裂变酵母中,当缺少Epe1脱甲基酶时,H3K9me异性染色体是可遗传的.
- 可遗传的异性染色体可能导致表皮变异,影响没有DNA变化的表型.
研究的目的:
- 调查是否依赖于异性染色体的表皮细胞对环境应激产生抗性.
- 确定表观遗传过程在野生类细胞中促进表型可塑性的作用.
- 探索异色素介导的沉默和对咖啡因和抗真菌剂的耐药性之间的联系.
主要方法:
- 培养具有可杀性咖啡因水平的裂变酵母,以选择耐药的表皮剂.
- 在耐药分离物中分析异色素的形成和基因表达.
- 进行向的异色素诱导以确认基因沉默机制.
主要成果:
- 在值咖啡因暴露下,裂变酵母中产生了抗咖啡因的表位剂.
- 这些隔离物表现出明显的异色素岛屿,减少关键基因的表达.
- 强迫的异性染色体形成证实耐药性是由于基因沉默.
- 咖啡因改变了抗沉声因子Epe1和Mst2基因组乙转移酶.
结论:
- 表观遗传过程,特别是异染色体依赖的表观突变,可以在没有遗传改变的情况下适应环境挑战.
- 这种表观遗传机制作为一种暂时适应的注策略.
- 可遗传的异染色质介导沉默可能会导致病原体对抗真菌剂的耐药性.
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