Maternal SMCHD1 regulates Hox gene expression and patterning in the mouse embryo.
Maternal SMCHD1 regulates Hox gene expression and patterning in the mouse embryo.
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DOI：
10.1038/s41467-022-32057-x
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发表时间：
2022-07-25
影响因子：
16.6
通讯作者：
Blewitt, Marnie E
中科院分区：
文献类型：
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作者：
Benetti, Natalia;Gouil, Quentin;Tapia Del Fierro, Andres;Beck, Tamara;Breslin, Kelsey;Keniry, Andrew;McGlinn, Edwina;Blewitt, Marnie E
父母将遗传和表观遗传信息传递给他们的后代。母体效应基因调控子代表观基因组，保证子代正常发育。在这里，我们报告的表观遗传调节SMCHD 1有一个母亲的影响Hox基因的表达和骨骼模式。母体SMCHD 1存在于卵母细胞和植入前胚胎中，可防止植入后Hox基因的过早激活。如果没有母体SMCHD 1，胚胎中会发生高度渗透的后部同源异型转化。在整个早期胚胎发育过程中，Hox基因被来自卵母细胞的Polycomb标记H2 AK 119 ub和H3 K27 me 3修饰;然而，母体SMCHD 1的缺失不会耗尽这些标记。因此，我们建议母体SMCHD 1作用于Polycomb标记的下游，以建立持久的表观遗传沉默和适当的Hox基因表达所必需的染色质状态，随后在发育中的胚胎中。这是母体SMCHD 1在影响后代表型的长寿表观遗传效应中的显著作用。父母传递遗传和表观遗传信息给他们的后代，与母性效应基因的后代表观基因组的关键调节器。在这里，他们表明母体沉积的SMCHD 1对Hox基因表达和植入后发育过程中的脊椎图案具有长期影响。
Parents transmit genetic and epigenetic information to their offspring. Maternal effect genes regulate the offspring epigenome to ensure normal development. Here we report that the epigenetic regulator SMCHD1 has a maternal effect on Hox gene expression and skeletal patterning. Maternal SMCHD1, present in the oocyte and preimplantation embryo, prevents precocious activation of Hox genes post-implantation. Without maternal SMCHD1, highly penetrant posterior homeotic transformations occur in the embryo. Hox genes are decorated with Polycomb marks H2AK119ub and H3K27me3 from the oocyte throughout early embryonic development; however, loss of maternal SMCHD1 does not deplete these marks. Therefore, we propose maternal SMCHD1 acts downstream of Polycomb marks to establish a chromatin state necessary for persistent epigenetic silencing and appropriate Hox gene expression later in the developing embryo. This is a striking role for maternal SMCHD1 in long-lived epigenetic effects impacting offspring phenotype. Parents transmit both genetic and epigenetic information to their offspring, with maternal effect genes being critical regulators of the offspring epigenome. Here they show that maternally deposited SMCHD1 has long-lasting effects on Hox gene expression and vertebral patterning during post-implantation development.