National Institute of Biological Sciences, Zhongguancun Life Science Park, Beijing, China.
Dev Dyn. 2012 Mar;241(3):455-64. doi: 10.1002/dvdy.23730. Epub 2012 Jan 12.
The p55 family WD40 repeat-containing histone chaperone proteins are components of several chromatin regulatory complexes (such as PRC2, NURF and CAF-1) and interact with histone H4, yet their functional relevance in vivo is unclear.
Here we use Drosophila as a genetic model to dissect the function of p55/Caf1 during development. In agree with a recent report, we find that p55 is essential for Drosophila development and is required for cell proliferation and viability. However, our data further demonstrate that histone H3K27 di-/tri-methylation and PRC2-mediated gene silencing still occur normally when p55 is missing. p55 is also implicated in bridging chromatin regulatory complexes to the chromatin by binding to histone H4, but we find that a transgene of p55 whose binding pocket is disrupted could still functionally substitute the wild-type p55 for the survival.
Our studies suggest that p55 is not crucial for PRC2-mediated gene silencing in vivo, and the vital function of p55 is probably not dependent on its interaction with histone H4.
p55 家族 WD40 重复结构域组蛋白伴侣蛋白是多个染色质调控复合物(如 PRC2、NURF 和 CAF-1)的组成部分,与组蛋白 H4 相互作用,但它们在体内的功能相关性尚不清楚。
在这里,我们使用果蝇作为遗传模型来解析 p55/Caf1 在发育过程中的功能。与最近的一份报告一致,我们发现 p55 对果蝇的发育是必需的,并且是细胞增殖和存活所必需的。然而,我们的数据进一步表明,当 p55 缺失时,H3K27 二甲基化和三甲基化以及 PRC2 介导的基因沉默仍然正常发生。p55 还涉及通过与组蛋白 H4 结合将染色质调控复合物桥接到染色质上,但我们发现,其结合口袋被破坏的 p55 转基因仍然可以替代野生型 p55 发挥功能,以维持细胞存活。
我们的研究表明,p55 对于体内 PRC2 介导的基因沉默不是至关重要的,p55 的重要功能可能不依赖于其与组蛋白 H4 的相互作用。