在Schizosaccharomyces pombe中,Set1,Clr4和Lsd1/2之间的交叉调节
Haoran Liu1, Bahjat Fadi Marayati2, David de la Cerda1
1Department of Biology, Wake Forest University, Winston-Salem, North Carolina, United States of America.
PLoS genetics
|January 5, 2024
概括
基斯调节剂Set1和Clr4对Lsd1/2脱甲基酶的蛋白质水平进行交叉调节. 这种调节对于动态色素格局和在裂变酵母中的热应激期间的差异性基因表达至关重要.
科学领域:
- 表观遗传学和染色体调节
- 控制基因表达 控制基因表达
- 历史蛋白修饰的动态
背景情况:
- 细胞染色体存在于沉默的异性染色体或活跃的细胞染色体,控制基因可访问性.
- 设置1 (H3K4甲基转移酶) 和Clr4 (H3K9甲基转移酶) 建立了独特的基因组甲基化标记.
- Lsd1和Lsd2是针对H3K4和H3K9的保守脱甲基酶,对于维持甲基化模式至关重要.
研究的目的:
- 为了研究基因组甲基转移酶 (Set1,Clr4) 和脱甲基酶 (Lsd1,Lsd2) 之间的交叉调节.
- 阐明控制这些关键酶的信号传递和相互调节的机制.
- 了解这些相互作用在染色质动态和基因表达中的作用,特别是在压力下.
主要方法:
- 使用C端截断突变体 (lsd1-ΔHMG,lsd2-ΔC) 来评估染色体结合能力.
- 确定了Lsd1/2和CLRC (Raf2) 和COMPASS (Swd2) 的子单元之间的蛋白质-蛋白质相互作用.
- 研究了Clr4和Set1通过ubiquitin-proteasome通路对Lsd1/2蛋白水平的影响,包括在热应激期间.
主要成果:
- 截断突变物损害了Lsd1/2染色体结合,但没有破坏复合体的完整性.
- 已确立Lsd1/2与Clr4和Set1复合物的组成部分之间的直接蛋白质相互作用.
- 证明Clr4和Set1通过蛋白质体降解对 Lsd1/2 蛋白质的稳定性进行相反调节.
- 在热应激期间显示了Lsd1/2蛋白水平的Set1-依赖上调,这对于压力诱导的基因表达至关重要.
结论:
- 支持一个交叉监管模型,其中Set1和Clr4控制Lsd1/2脱甲基酶水平.
- 这些甲基转移酶微调脱甲基酶的丰富性,以塑造动态的染色质景观.
- 这种调节对于适应性基因表达对热应激等环境挑战的反应至关重要.
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