Department of Bioinformational Pharmacology, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan.
Isotope Science Center, The University of Tokyo, Tokyo, 113-0032, Japan.
Commun Biol. 2020 Nov 30;3(1):725. doi: 10.1038/s42003-020-01456-5.
Temporal and spatial colinear expression of the Hox genes determines the specification of positional identities during vertebrate development. Post-translational modifications of histones contribute to transcriptional regulation. Lysine demethylase 7A (Kdm7a) demethylates lysine 9 or 27 di-methylation of histone H3 (H3K9me2, H3K27me2) and participates in the transcriptional activation of developmental genes. However, the role of Kdm7a during mouse embryonic development remains to be elucidated. Herein, we show that Kdm7a mouse exhibits an anterior homeotic transformation of the axial skeleton, including an increased number of presacral elements. Importantly, posterior Hox genes (caudally from Hox9) are specifically downregulated in the Kdm7a embryo, which correlates with increased levels of H3K9me2, not H3K27me2. These observations suggest that Kdm7a controls the transcription of posterior Hox genes, likely via its demethylating activity, and thereby regulating the murine anterior-posterior development. Such epigenetic regulatory mechanisms may be harnessed for proper control of coordinate body patterning in vertebrates.
时空共线性表达的 Hox 基因决定了脊椎动物发育过程中位置身份的特化。组蛋白的翻译后修饰有助于转录调控。赖氨酸去甲基酶 7A（Kdm7a）可以去除组蛋白 H3 的赖氨酸 9 或 27 位二甲基化（H3K9me2、H3K27me2），并参与发育基因的转录激活。然而，Kdm7a 在小鼠胚胎发育过程中的作用仍有待阐明。在此，我们发现 Kdm7a 小鼠表现出轴向骨骼的前同源性转化，包括前骶骨元素数量增加。重要的是，Kdm7a 胚胎中后部 Hox 基因（从 Hox9 开始）特异性下调，这与 H3K9me2 水平升高而非 H3K27me2 相关。这些观察结果表明，Kdm7a 通过其去甲基化活性控制后部 Hox 基因的转录，从而调节小鼠的前后发育。这种表观遗传调控机制可能被用于脊椎动物协调的身体模式形成的适当控制。
