The histone chaperone NASP maintains H3-H4 reservoirs in the early Drosophila embryo.
The histone chaperone NASP maintains H3-H4 reservoirs in the early Drosophila embryo.
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DOI：
10.1371/journal.pgen.1010682
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发表时间：
2023-03
期刊：
影响因子：
4.5
通讯作者：
中科院分区：
文献类型：
--
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组蛋白对于染色质包装至关重要，并且必须严格调节组蛋白的供应，因为过量的组蛋白是有毒的。然而，为了驱动早期胚胎的快速细胞周期，多余的组蛋白被母体沉积。因此，可溶性组蛋白必须由组蛋白伴侣缓冲，但稳定果蝇胚胎中可溶性 H3-H4 池所需的伴侣尚未确定。在这里，我们证明 CG8223（NASP 的果蝇同源物）是早期胚胎中 H3-H4 特异性伴侣。我们证明，虽然 NASP 无效突变体在果蝇中是可行的，但 NASP 是母体效应基因。 NASP 突变母体产下的胚胎孵化率降低，并在早期胚胎发生中表现出缺陷。至关重要的是，可溶性 H3-H4 池在 NASP 突变母体产下的胚胎中被降解。我们的工作将 NASP 确定为果蝇胚胎中关键的 H3-H4 组蛋白伴侣。组蛋白 H2A、H2B、H3 和 H4 是 DNA 包装基本单位所需的小蛋白质。组蛋白的过度表达或耗尽对细胞有毒，因此组蛋白的合成、运输、储存和沉积到染色质中需要仔细调节。组蛋白伴侣几乎影响组蛋白代谢的所有方面，包括组蛋白储存。在果蝇发育过程中，过量的组蛋白由母源提供给早期胚胎，以驱动早期的快速核周期。为了防止组蛋白降解，组蛋白的母体沉积必须通过组蛋白伴侣来稳定。然而迄今为止，在早期胚胎中稳定 H3-H4 的组蛋白伴侣仍然未知。基于序列、结构和功能，我们表明NASP的果蝇同源物是果蝇早期胚胎中关键的H3-H4组蛋白伴侣。 NASP 需要稳定母体沉积的 H3-H4 供应，从而促进早期胚胎发生。虽然 NASP 不是必需基因，但 NASP 突变母亲产下的胚胎在胚胎发生中表现出一些缺陷。我们的工作定义了早期果蝇胚胎中 H3 和 H4 储存和稳定性的基本方面。
Histones are essential for chromatin packaging, and histone supply must be tightly regulated as excess histones are toxic. To drive the rapid cell cycles of the early embryo, however, excess histones are maternally deposited. Therefore, soluble histones must be buffered by histone chaperones, but the chaperone necessary to stabilize soluble H3-H4 pools in the Drosophila embryo has yet to be identified. Here, we show that CG8223, the Drosophila homolog of NASP, is a H3-H4-specific chaperone in the early embryo. We demonstrate that, while a NASP null mutant is viable in Drosophila, NASP is a maternal effect gene. Embryos laid by NASP mutant mothers have a reduced rate of hatching and show defects in early embryogenesis. Critically, soluble H3-H4 pools are degraded in embryos laid by NASP mutant mothers. Our work identifies NASP as the critical H3-H4 histone chaperone in the Drosophila embryo. Histones H2A, H2B, H3, and H4 are small proteins required for the basic unit of DNA packaging. Overexpression or depletion of histones is toxic to cells, therefore histone synthesis, trafficking, storage and deposition into chromatin requires careful regulation. Histone chaperones influence nearly all aspects of histone metabolism, including histone storage. During Drosophila development, excess histones are maternally provided to the early embryo to drive the early rapid nuclear cycles. To prevent histone degradation, maternal deposits of histones must be stabilized by a histone chaperone. To date, however, the histone chaperone that stabilizes H3-H4 in the early embryo has remained unknown. Based on sequence, structure and function, we show that the Drosophila homolog of NASP is the critical H3-H4 histone chaperone in the Drosophila early embryo. NASP is required to stabilize the maternally deposited H3-H4 supply that fuels early embryogenesis. While NASP is not an essential gene, embryos laid by NASP mutant mothers show several defects in embryogenesis. Our work defines fundamental aspects of H3 and H4 storage and stability in the early Drosophila embryo.
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影响因子：
14.9
作者：
Bao, Hongyu;Carraro, Massimo;Flury, Valentin;Liu, Yanhong;Luo, Min;Chen, Liu;Groth, Anja;Huang, Hongda
通讯作者：
Huang, Hongda
抑制组蛋白 H3-H4 伴侣通路可通过 H2B 损失挽救线虫不育性
影响因子：
4.5
作者：
通讯作者：
--
影响因子：
--
作者：
Gratz SJ;Rubinstein CD;Harrison MM;Wildonger J;O'Connor-Giles KM
通讯作者：
O'Connor-Giles KM
影响因子：
5
作者：
Honorato RV;Koukos PI;Jiménez-García B;Tsaregorodtsev A;Verlato M;Giachetti A;Rosato A;Bonvin AMJJ
通讯作者：
Bonvin AMJJ
影响因子：
2.7
作者：
AMBROSIO, L;SCHEDL, P
通讯作者：
SCHEDL, P