Martini Davide, Digregorio Matteo, Voto Ilaria Anna Pia, Morabito Giuseppe, Degl'Innocenti Andrea, Giudetti Guido, Giannaccini Martina, Andreazzoli Massimiliano
Department of Biology, University of Pisa, Pisa, Italy.
Dev Dyn. 2024 May;253(5):508-518. doi: 10.1002/dvdy.670. Epub 2023 Nov 1.
Post-translational histone modifications are among the most common epigenetic modifications that orchestrate gene expression, playing a pivotal role during embryonic development and in various pathological conditions. Among histone lysine demethylases, KDM7A, also known as KIAA1718 or JHDM1D, catalyzes the demethylation of H3K9me1/2 and H3K27me1/2, leading to transcriptional regulation. Previous data suggest that KDM7A plays a central role in several biological processes, including cell proliferation, commitment, differentiation, apoptosis, and maintenance. However, information on the expression pattern of KDM7A in whole organisms is limited, and its functional role is still unclear.
In Xenopus development, kdm7a is expressed early, undergoing spatiotemporal regulation in various organs and tissues, including the central nervous system and the eye. Focusing on retinal development, we found that kdm7a overexpression does not affect the expression of genes critically involved in early neural development and eye-field specification, whereas unbalances the distribution of neural cell subtypes in the mature retina by disfavoring the development of ganglion cells while promoting that of horizontal cells.
Kdm7a is dynamically expressed during embryonic development, and its overexpression influences late retinal development, suggesting a potential involvement in the molecular machinery regulating the spatiotemporally ordered generation of retinal neuronal subtypes.
翻译后组蛋白修饰是最常见的表观遗传修饰之一，可协调基因表达，在胚胎发育和各种病理状态中起关键作用。在组蛋白赖氨酸去甲基化酶中，KDM7A，也称为KIAA1718或JHDM1D，催化H3K9me1/2和H3K27me1/2的去甲基化，从而导致转录调控。先前的数据表明，KDM7A在包括细胞增殖、定向、分化、凋亡和维持在内的多个生物学过程中起核心作用。然而，关于KDM7A在整个生物体中的表达模式的信息有限，其功能作用仍不清楚。
在非洲爪蟾发育过程中，kdm7a早期表达，在包括中枢神经系统和眼睛在内的各种器官和组织中经历时空调控。聚焦于视网膜发育，我们发现kdm7a过表达不影响早期神经发育和眼场特化关键基因的表达，而通过不利于神经节细胞的发育而促进水平细胞的发育，从而使成熟视网膜中神经细胞亚型的分布失衡。
Kdm7a在胚胎发育过程中动态表达，其过表达影响视网膜后期发育，提示其可能参与调控视网膜神经元亚型时空有序生成的分子机制。
