Ohguchi Yasuyo, Ohguchi Hiroto
Division of Disease Epigenetics, Institute of Resource Development and Analysis, Kumamoto University, Kumamoto 860-0811, Japan.
Cancers (Basel). 2022 Jul 4;14(13):3270. doi: 10.3390/cancers14133270.
Epigenetic modifications are crucial for chromatin remodeling and transcriptional regulation. Post-translational modifications of histones are epigenetic processes that are fine-tuned by writer and eraser enzymes, and the disorganization of these enzymes alters the cellular state, resulting in human diseases. The KDM5 family is an enzymatic family that removes di- and tri-methyl groups (me2 and me3) from lysine 4 of histone H3 (H3K4), and its dysregulation has been implicated in cancer. Although H3K4me3 is an active chromatin marker, KDM5 proteins serve as not only transcriptional repressors but also transcriptional activators in a demethylase-dependent or -independent manner in different contexts. Notably, KDM5 proteins regulate the H3K4 methylation cycle required for active transcription. Here, we review the recent findings regarding the mechanisms of transcriptional regulation mediated by KDM5 in various contexts, with a focus on cancer, and further shed light on the potential of targeting KDM5 for cancer therapy.
表观遗传修饰对于染色质重塑和转录调控至关重要。组蛋白的翻译后修饰是由书写酶和擦除酶进行微调的表观遗传过程，这些酶的紊乱会改变细胞状态，导致人类疾病。KDM5家族是一个酶家族，可从组蛋白H3（H3K4）的赖氨酸4上去除二甲基和三甲基基团（me2和me3），其失调与癌症有关。尽管H3K4me3是一种活跃的染色质标记，但在不同情况下，KDM5蛋白不仅以脱甲基酶依赖性或非依赖性方式作为转录抑制因子，还作为转录激活因子。值得注意的是，KDM5蛋白调节活跃转录所需的H3K4甲基化循环。在此，我们综述了关于KDM5在各种情况下介导转录调控机制的最新发现，重点是癌症，并进一步阐明了靶向KDM5进行癌症治疗的潜力。
