Maintaining a proper supply of soluble histones throughout the cell cycle is important to ensure chromatin and genome stability. Following their synthesis, histones undergo a series of maturation steps to prepare them for deposition onto chromatin. Here, we identify the lysine demethylase JMJD1B as a novel player in the maturation cascade that contributes to regulate histone provision. We find that depletion of JMJD1B increases the protein levels of the histone chaperone tNASP leading to an accumulation of newly synthesized histones H3 and H4 at early steps of the histone maturation cascade, which perturbs chromatin assembly. Furthermore, we find a high rate of JMJD1B mutations in cancer patients, and a correlation with genomic instability. Our data support a role for JMJD1B in fine-tuning histone supply to maintain genome integrity, opening novel avenues for cancer therapeutics.

中文翻译：

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JMJD1B，组蛋白H3和H4加工中的新型参与者，可确保基因组稳定性

在整个细胞周期中维持可溶性组蛋白的适当供应对于确保染色质和基因组稳定性至关重要。合成后，组蛋白要经历一系列成熟步骤，以准备将其沉积到染色质上。在这里，我们确定赖氨酸脱甲基酶JMJD1B是成熟级联反应中的一个新型参与者，它有助于调节组蛋白的提供。我们发现，JMJD1B的消耗增加了组蛋白伴侣tNASP的蛋白质水平，导致在组蛋白成熟级联的早期步骤中新合成的组蛋白H3和H4的积累，这扰乱了染色质的组装。此外，我们发现癌症患者中JMJD1B突变的发生率很高，并且与基因组不稳定性相关。我们的数据支持JMJD1B在微调组蛋白供应以维持基因组完整性方面的作用，