Comparison of gene expression profiles between wild-type and Kdm7a mutant embryos

Temporal and spatial colinear expression of Hox genes determines the specification of positional identities of the embryo. Post-translational modifications of histones contribute to transcriptional regulation, and are required for proper control of biological processes, including differentiation and development. Lysine demethylase 7A (Kdm7a) demethylates lysine 9 di-methylation of histone H3 (H3K9me2) and participates in transcriptional activation of developmental genes. However, the role of Kdm7a during mouse embryonic development remains to be elucidated. Here, we show that Kdm7a-/- mice exhibit anterior homeotic transformation of the axial skeleton (i.e. an increase in the number of presacral elements). Importantly, posterior Hox genes (caudally from Hox9) are specifically down-regulated in Kdm7a-/- embryos, which correlate with increased levels of H3K9me2. Taken together, these data suggest that Kdm7a is able to control transcription of posterior Hox genes, likely through its demethylating activity, and thereby regulating anterior-posterior development in mice. Total 12 samples were derived from [1] wild-type E9.5 embryos , [2] Kdm7a mutant E9.5 embryos, [3] wild-type E10.5 embryos, [4] Kdm7a mutant E10.5 embryos (n=3 for each condition).Hox基因（Homeobox genes）的时空共线性表达决定了胚胎位置特性的特化。组蛋白的翻译后修饰参与转录调控，且对于正确调控包括细胞分化与个体发育在内的生物学过程至关重要。赖氨酸去甲基化酶7A（Kdm7a）可催化组蛋白H3第9位赖氨酸二甲基化（H3K9me2）的去甲基化反应，并参与发育相关基因的转录激活。然而，Kdm7a在小鼠胚胎发育过程中的具体功能仍有待阐明。本研究发现，Kdm7a基因敲除（Kdm7a⁻/⁻）小鼠表现出轴骨的前部同源异型转化，即骶前结构数量增加。值得注意的是，在Kdm7a⁻/⁻胚胎中，Hox9之后尾部方向的后部Hox基因表达被特异性下调，这与H3K9me2水平的升高显著相关。综上，上述实验数据表明，Kdm7a可通过其去甲基化活性调控后部Hox基因的转录，进而调控小鼠胚胎的前后轴发育。本数据集共包含12个样本，分别取自[1]野生型E9.5胚胎、[2]Kdm7a突变型E9.5胚胎、[3]野生型E10.5胚胎以及[4]Kdm7a突变型E10.5胚胎，每组条件设置3个生物学重复（n=3）。