1,6-hexanediol rapidly immobilizes and condenses chromatin in living human cells.

1,6-hexanediol rapidly immobilizes and condenses chromatin in living human cells.
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DOI:
10.26508/lsa.202001005
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发表时间:
2021-04
影响因子:
4.4
通讯作者:
Maeshima K
Maeshima K
中科院分区:
生物学2区
文献类型:
--
作者:
Itoh Y;Iida S;Tamura S;Nagashima R;Shiraki K;Goto T;Hibino K;Ide S;Maeshima K

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醇,1,6-己二醇,广泛用于熔化液-液相分离形成的液滴;然而,它也可以通过固定和浓缩染色质来严重影响细胞。通过液-液相分离在电池内部形成的液滴保持无膜冷凝物/主体(或隔室)。这些液滴对于浓缩某些分子和促进细胞功能的时空调节是重要的。1,6-己二醇(1,6-HD)是一种脂肪醇,可抑制液滴形成(液滴熔化活性)所需的弱疏水性蛋白质-蛋白质/蛋白质-RNA相互作用,在此用于阐明细胞质/核凝聚物/小体的形成过程。然而,1,6-HD对活细胞中染色质的影响仍不清楚。我们发现,1,6-HD大大抑制染色质运动和超浓缩染色质在人类细胞中,通过使用活细胞单核小体成像,检测染色质状态的变化。这些作用以剂量依赖性方式增强。染色质被5%或更高浓度的1,6-HD“冷冻”。1,6-HD极大地促进了阳离子依赖的染色质体外凝聚。1,6-HD的这种作用不同于其对液滴的熔化活性。酒精,如1,6-HD,似乎可以去除染色质周围的水分子并局部浓缩染色质。因此,当这些液滴与染色质结合时,应仔细解释或重新考虑使用1,6-HD获得的液滴结果。
Alcohol, 1,6-hexanediol, is widely used for melting liquid droplets formed by liquid0–liquid phase separation; however, it can also seriously affect cells by immobilizing and condensing chromatin. Liquid droplets formed inside the cell by liquid–liquid phase separation maintain membrane-less condensates/bodies (or compartments). These droplets are important for concentrating certain molecules and facilitating spatiotemporal regulation of cellular functions. 1,6-hexanediol (1,6-HD), an aliphatic alcohol, inhibits weak hydrophobic protein–protein/protein-RNA interactions required for the droplet formation (droplet melting activity) and is used here to elucidate the formation process of cytoplasmic/nuclear condensates/bodies. However, the effect of 1,6-HD on chromatin in living cells remains unclear. We found that 1,6-HD drastically suppresses chromatin motion and hyper-condenses chromatin in human cells by using live-cell single-nucleosome imaging, which detects changes in the state of chromatin. These effects were enhanced in a dose-dependent manner. Chromatin was “frozen” by 5%, or higher, concentrations of 1,6-HD. 1,6-HD greatly facilitated cation-dependent chromatin condensation in vitro. This 1,6-HD action is distinct from its melting activity of liquid droplets. Alcohols, such as 1,6-HD, appear to remove water molecules around chromatin and locally condense chromatin. Therefore, liquid droplet results obtained using 1,6-HD should be carefully interpreted or reconsidered when these droplets are associated with chromatin.
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