背景:翻译后组蛋白修饰是协调基因表达的最常见的表观遗传修饰之一,在胚胎发育和各种病理状况中起着关键作用。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,导致转录调控。以前的数据表明,KDM7A在几个生物过程中起着核心作用,包括细胞增殖,承诺,分化,凋亡,和维护。然而,关于KDM7A在整个生物体中的表达模式的信息是有限的,其功能作用尚不清楚。
结果:在非洲爪鱼发育中,kdm7a表示得早,在各种器官和组织中进行时空调节,包括中枢神经系统和眼睛.专注于视网膜发育,我们发现kdm7a过表达不影响严重参与早期神经发育和眼场规范的基因的表达,而通过促进水平细胞的发育,不利于神经节细胞的发育,从而使成熟视网膜中神经细胞亚型的分布失衡。
结论:Kdm7a在胚胎发育过程中动态表达,它的过度表达影响视网膜晚期发育,提示可能参与调节视网膜神经元亚型时空有序生成的分子机制。
BACKGROUND: 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.
RESULTS: 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.
CONCLUSIONS: 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.