Epigenetic regulation is important for establishing lineage-specific gene expression during early development. Although signaling pathways have been well-studied for regulation of trophectoderm reprogramming, epigenetic regulation of trophectodermal genes with histone modification dynamics have been poorly understood. Here, we identify that plant homeodomain finger protein 6 (PHF6) is a key epigenetic regulator for activation of trophectodermal genes using RNA-sequencing and ChIP assays. PHF6 acts as an E3 ubiquitin ligase for ubiquitination of H2BK120 (H2BK120ub) via its extended plant homeodomain 1 (PHD1), while the extended PHD2 of PHF6 recognizes acetylation of H2BK12 (H2BK12Ac). Intriguingly, the recognition of H2BK12Ac by PHF6 is important for exerting its E3 ubiquitin ligase activity for H2BK120ub. Together, our data provide evidence that PHF6 is crucial for epigenetic regulation of trophectodermal gene expression by linking H2BK12Ac to H2BK120ub modification.

中文翻译：

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染色质结合蛋白PHF6通过H2BK12Ac识别作用作为H2BK120的E3泛素连接酶来激活滋养外胚层基因。

表观遗传调控对于在早期发育过程中建立谱系特异性基因表达很重要。尽管已经充分研究了调节滋养外胚层重编程的信号传导途径，但是对具有组蛋白修饰动力学的滋养外胚层基因的表观遗传调控知之甚少。在这里，我们确定植物同源域手指蛋白6（PHF6）是使用RNA测序和ChIP分析激活滋养表皮基因的关键表观遗传调控因子。PHF6充当E3泛素连接酶，通过其扩展的植物同源结构域1（PHD1）进行H2BK120（H2BK120ub）的泛素化，而PHF6的扩展PHD2识别H2BK12（H2BK12Ac）的乙酰化。有趣的是，PHF6对H2BK12Ac的识别对于发挥H3BK120ub的E3泛素连接酶活性很重要。一起，