Developmentally regulated H2Av buffering via dynamic sequestration to lipid droplets in Drosophila embryos
Developmentally regulated H2Av buffering via dynamic sequestration to lipid droplets in Drosophila embryos
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DOI：
10.7554/elife.36021
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发表时间：
2018-07-25
期刊：
影响因子：
7.7
通讯作者：
Welte, Michael Andreas
中科院分区：
文献类型：
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作者：
Johnson, Matthew Richard;Stephenson, Roxan Amanda;Welte, Michael Andreas
调节核组蛋白平衡对于生存至关重要，但在早期黑腹果蝇胚胎中，体细胞中采用的许多调节策略是不可用的。以前的工作表明，脂滴（LD）缓冲组蛋白变体H2Av的核积累。在这里，我们阐明了缓冲机制，并证明它是发展控制。使用实时成像，我们发现H2Av在LD之间持续交换。我们的数据表明，H2Av在细胞核中积累的主要驱动力是H2Av在细胞质中的丰度，并且LD结合通过限制该细胞质池而在动力学上减慢核输入。细胞核H2Av的积累确实受到整体缓冲能力的反向调节。LD之间的组蛋白交换突然停止在囊胚中期过渡，大概是为了让规范的监管机制接管。这些发现为LD作为蛋白质稳态调节剂的新兴作用提供了机制基础，并证明LD可以控制发育进程。
Regulating nuclear histone balance is essential for survival, yet in early Drosophila melanogaster embryos many regulatory strategies employed in somatic cells are unavailable. Previous work had suggested that lipid droplets (LDs) buffer nuclear accumulation of the histone variant H2Av. Here, we elucidate the buffering mechanism and demonstrate that it is developmentally controlled. Using live imaging, we find that H2Av continuously exchanges between LDs. Our data suggest that the major driving force for H2Av accumulation in nuclei is H2Av abundance in the cytoplasm and that LD binding slows nuclear import kinetically, by limiting this cytoplasmic pool. Nuclear H2Av accumulation is indeed inversely regulated by overall buffering capacity. Histone exchange between LDs abruptly ceases during the midblastula transition, presumably to allow canonical regulatory mechanisms to take over. These findings provide a mechanistic basis for the emerging role of LDs as regulators of protein homeostasis and demonstrate that LDs can control developmental progression.