Chromatin modulation provides a key checkpoint for controlling cell cycle regulated gene networks. The replicative canonical histone genes are one such gene family under tight regulation during cell division. These genes are most highly expressed during S phase when histones are needed to chromatinize the new DNA template. While this fact has been known for a while, limited knowledge exists about the specific chromatin regulators controlling their temporal expression during cell cycle. Since histones and their associated mutations are emerging as major players in diseases such as cancer, identifying the chromatin factors modulating their expression is critical. The histone lysine tri-demethylase KDM4A is regulated over cell cycle and plays a direct role in DNA replication timing, site-specific rereplication, and DNA amplifications during S phase. Here, we establish an unappreciated role for the catalytically active KDM4A in directly regulating canonical replicative histone gene networks during cell cycle. Of interest, we further demonstrate that KDM4A interacts with proteins controlling histone expression and RNA processing (i.e., hnRNPUL1 and FUS/TLS). Together, this study provides a new function for KDM4A in modulating canonical histone gene expression.

染色质调节为控制细胞周期调控的基因网络提供了一个关键的检查点。复制经典组蛋白基因就是这样一个在细胞分裂过程中受到严格调控的基因家族。当需要组蛋白对新 DNA 模板进行染色时，这些基因在 S 期表达最高。虽然这一事实早已为人所知，但关于在细胞周期中控制其时间表达的特定染色质调节因子的知识有限。由于组蛋白及其相关突变正在成为癌症等疾病的主要参与者，因此确定调节其表达的染色质因子至关重要。组蛋白赖氨酸三脱甲基酶 KDM4A 在细胞周期中受到调节，并在 S 期的 DNA 复制时间、位点特异性再复制和 DNA 扩增中发挥直接作用。在这里，我们建立了催化活性 KDM4A 在细胞周期中直接调节经典复制组蛋白基因网络的未被重视的作用。有趣的是，我们进一步证明 KDM4A 与控制组蛋白表达和 RNA 加工的蛋白质相互作用。我。例如，hnRNPUL1 和 FUS/TLS）。总之，这项研究为 KDM4A 在调节经典组蛋白基因表达方面提供了新功能。