Drosophila lipid droplets buffer the H2Av supply to protect early embryonic development.
Drosophila lipid droplets buffer the H2Av supply to protect early embryonic development.
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DOI：
10.1016/j.cub.2014.05.022
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发表时间：
2014-07-07
期刊：
影响因子：
9.2
通讯作者：
Welte, Michael A.
中科院分区：
文献类型：
--
作者：
Li, Zhihuan;Johnson, Matthew R.;Ke, Zhonghe;Chen, Lili;Welte, Michael A.
将DNA组装成染色质需要一个微妙的平衡过程，因为组蛋白的缺乏和过剩都会严重扰乱染色质的功能。特别是，细胞需要仔细控制组蛋白的化学计量：如果不同类型的组蛋白以不平衡的方式结合到染色质中，可能会导致基因表达改变、有丝分裂错误和死亡。个体核心组蛋白之间以及核心组蛋白和组蛋白变体之间的平衡都是至关重要的。在这里，我们发现在果蝇早期胚胎中，细胞核中的组蛋白平衡受到脂滴、细胞质脂肪储存细胞器的调节。以前已知脂滴在组蛋白的长期存储中起作用：新生的胚胎包含大量在卵子发生过程中产生的过剩组蛋白，母体供应的核心组蛋白H_2A和组蛋白变体H_2Av通过新的蛋白质Jabba锚定在脂滴上。我们发现，在这些胚胎中，新的H_2A和H_2Av的合成是不平衡的，新产生的H_2Av可以被招募到脂滴中。当突变的JABBA破坏液滴的固存时，胚胎表现出细胞核中H_2Av/H_2A比率升高，以及有丝分裂缺陷，活力降低，并对H_2Av过度表达敏感。我们认为，在果蝇胚胎中，脂滴作为组蛋白的缓冲区，不仅存储了母体组蛋白以支持早期的细胞周期，而且暂时隔离了过量产生的H_2Av，从而确保了细胞核中适当的组蛋白平衡。
Assembly of DNA into chromatin requires a delicate balancing act, as both dearth and excess of histones severely disrupts chromatin function. In particular, cells need to carefully control histone stoichiometry: if different types of histones are incorporated into chromatin in an imbalanced manner, it can lead to altered gene expression, mitotic errors, and death. Both the balance between individual core histones and between core histones and histone variants is critical. Here, we find that in early Drosophila embryos histone balance in the nuclei is regulated by lipid droplets, cytoplasmic fat storage organelles. Lipid droplets were previously known to function in long-term histone storage: newly laid embryos contain large amounts of excess histones generated during oogenesis, and the maternal supplies of core histone H2A and the histone variant H2Av are anchored to lipid droplets via the novel protein Jabba. We find that in these embryos synthesis of new H2A and H2Av is imbalanced and that newly produced H2Av can be recruited to lipid droplets. When droplet sequestration is disrupted by mutating Jabba, embryos display an elevated H2Av/H2A ratio in nuclei as well as mitotic defects, reduced viability, and hypersensitivity to H2Av overexpression. We propose that in Drosophila embryos lipid droplets serve as a histone buffer, not only storing maternal histones to support the early cell cycles, but also transiently sequestering H2Av produced in excess and thus ensuring proper histone balance in the nucleus.
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影响因子：
64.5
作者：
EDGAR, BA;SCHUBIGER, G
通讯作者：
SCHUBIGER, G
影响因子：
9.2
作者：
Li, Zhihuan;Thiel, Katharina;Thul, Peter J.;Beller, Mathias;Kuehnlein, Ronald P.;Welte, Michael A.
通讯作者：
Welte, Michael A.
影响因子：
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作者：
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通讯作者：
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影响因子：
3.3
作者：
Au, Wei-Chun;Crisp, Matthew J.;Basrai, Munira A.
通讯作者：
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影响因子：
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作者：
Beller, Mathias;Riedel, Dietmar;Kuehnlein, Ronald P.
通讯作者：
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