Fundación Ciencia & Vida, 7780272, Santiago, Chile.
Universidad San Sebastián, 7510156, Santiago, Chile.
Epigenetics Chromatin. 2020 Feb 18;13(1):6. doi: 10.1186/s13072-020-00331-1.
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.
在细胞周期中保持适当的可溶性组蛋白供应对于确保染色质和基因组稳定性非常重要。在合成后，组蛋白要经过一系列成熟步骤的处理，才能准备好沉积到染色质上。
在这里，我们确定赖氨酸去甲基酶 JMJD1B 是成熟级联中的一个新成员，它有助于调节组蛋白的供应。我们发现 JMJD1B 的耗竭会增加组蛋白伴侣 tNASP 的蛋白水平，导致组蛋白 H3 和 H4 的新合成在组蛋白成熟级联的早期步骤中积累，从而扰乱染色质组装。此外，我们在癌症患者中发现了 JMJD1B 突变的高发率，并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，为癌症治疗开辟了新的途径。
