Creative Research Initiatives Center for Epigenetic Code and Diseases, Department of Biological Sciences, Seoul National University, Seoul 08826, South Korea.
Graduate School of Cancer Science and Policy, Research Institute, National Cancer Center, Goyang 10408, South Korea.
Nucleic Acids Res. 2020 Sep 18;48(16):9037-9052. doi: 10.1093/nar/gkaa626.
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.
表观遗传调控对于早期发育过程中建立谱系特异性基因表达非常重要。尽管信号通路已被很好地研究用于滋养外胚层重编程的调控，但滋养外胚层基因的表观遗传调控与组蛋白修饰动力学仍知之甚少。在这里，我们使用 RNA 测序和 ChIP 分析鉴定出植物同源结构域指蛋白 6 (PHF6) 是激活滋养外胚层基因的关键表观遗传调控因子。PHF6 通过其扩展的植物同源结构域 1 (PHD1) 作为 E3 泛素连接酶，对 H2BK120 (H2BK120ub) 进行泛素化，而 PHF6 的扩展 PHD2 识别 H2BK12 的乙酰化 (H2BK12Ac)。有趣的是，PHF6 对 H2BK12Ac 的识别对于发挥其 E3 泛素连接酶活性以进行 H2BK120ub 修饰非常重要。总之，我们的数据提供了证据表明，PHF6 通过将 H2BK12Ac 与 H2BK120ub 修饰联系起来，对于滋养外胚层基因表达的表观遗传调控至关重要。
