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.

Hox基因的时空共线性表达决定了脊椎动物发育过程中位置身份的规范。组蛋白的翻译后修饰有助于转录调控。赖氨酸脱甲基酶7A（Kdm7a）使组蛋白H3（H3K9me2，H3K27me2）的赖氨酸9或27二甲基化脱甲基，并参与发育基因的转录激活。但是，Kdm7a在小鼠胚胎发育中的作用仍有待阐明。在这里，我们显示Kdm7a ^-/-小鼠表现出轴向骨骼的前同种异体转换，包括增加的s前元件数量。重要的是，后Hox基因（尾部来自Hox9）在Kdm7a ^-/-胚胎中特别下调，这与H3K9me2（而非H3K27me2）水平升高相关。这些观察结果表明，Kdm7a可能通过其去甲基化活性来控制后Hox基因的转录，从而调节鼠的前后发育。可以利用这样的表观遗传调控机制来适当地控制脊椎动物的协调体模式。