CHD1 acts via the Hmgpi pathway to regulate mouse early embryogenesis
CHD1 acts via the Hmgpi pathway to regulate mouse early embryogenesis
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DOI：
10.1242/dev.120493
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发表时间：
2015-07-01
期刊：
影响因子：
4.6
通讯作者：
Minami, Naojiro
中科院分区：
文献类型：
--
作者：
Suzuki, Shinnosuke;Nozawa, Yusuke;Minami, Naojiro
蛋白质CHD1是ATP酶依赖性染色质重塑因子家族的成员。CHD1，识别三甲基化组蛋白H3赖氨酸4，已经涉及从酵母到人类的生物体中的转录激活。它是前mRNA成熟、维持小鼠胚胎干细胞多能性和小鼠外胚层快速生长所必需的。然而，CHD1在小鼠植入前胚胎中的功能尚未被研究。在这里，我们表明，CHD1功能的丧失导致胚胎着床后死亡。在通过siRNA显微注射靶向Chd 1的小鼠胚胎中，细胞命运规范Pou5f1（也称为Oct4），Nanog和Cdx 2的关键调节因子的表达显着降低，从中期植入前基因激活（MGA）开始。此外，Hmgpi和Klf5的表达，调节Pou5f1，Nanog和Cdx2，也显着抑制合子基因激活（ZGA）。在Chd 1敲除胚胎中Hmgpi表达的抑制持续到囊胚期，而Klf 5表达的抑制在桑椹胚期被解除。接下来，我们通过Hmgpi mRNA显微注射在Chd1敲低的胚胎中挽救了HMGPI的表达。因此，Pou5f1，Nanog和Cdx2的表达在MGA恢复和活的后代被回收。这些发现表明CHD1通过激活ZGA的Hmgpi在小鼠早期胚胎发生中起重要作用。
The protein CHD1 is a member of the family of ATPase-dependent chromatin remodeling factors. CHD1, which recognizes trimethylated histone H3 lysine 4, has been implicated in transcriptional activation in organisms ranging from yeast to humans. It is required for pre-mRNA maturation, maintenance of mouse embryonic stem cell pluripotency and rapid growth of the mouse epiblast. However, the function(s) of CHD1 in mouse preimplantation embryos has not yet been examined. Here, we show that loss of CHD1 function led to embryonic lethality after implantation. In mouse embryos in which Chd1 was targeted by siRNA microinjection, the expression of the key regulators of cell fate specification Pou5f1 (also known as Oct4), Nanog and Cdx2 was dramatically decreased, starting at mid-preimplantation gene activation (MGA). Moreover, expression of Hmgpi and Klf5, which regulate Pou5f1, Nanog and Cdx2, was also significantly suppressed at zygotic gene activation (ZGA). Suppression of Hmgpi expression in Chd1-knockdown embryos continued until the blastocyst stage, whereas suppression of Klf5 expression was relieved by the morula stage. Next, we rescued HMGPI expression via Hmgpi mRNA microinjection in Chd1-knockdown embryos. Consequently, Pou5f1, Nanog and Cdx2 expression was restored at MGA and live offspring were recovered. These findings indicate that CHD1 plays important roles in mouse early embryogenesis via activation of Hmgpi at ZGA.