Jacinto Filipe V, Benner Chris, Hetzer Martin W
Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, 92037 California, USA.
Genes Dev. 2015 Jun 15;29(12):1224-38. doi: 10.1101/gad.260919.115. Epub 2015 Jun 16.
Nucleoporins (Nups) are a family of proteins best known as the constituent building blocks of nuclear pore complexes (NPCs), membrane-embedded channels that mediate nuclear transport across the nuclear envelope. Recent evidence suggests that several Nups have additional roles in controlling the activation and silencing of developmental genes; however, the mechanistic details of these functions remain poorly understood. Here, we show that depletion of Nup153 in mouse embryonic stem cells (mESCs) causes the derepression of developmental genes and induction of early differentiation. This loss of stem cell identity is not associated with defects in the nuclear import of key pluripotency factors. Rather, Nup153 binds around the transcriptional start site (TSS) of developmental genes and mediates the recruitment of the polycomb-repressive complex 1 (PRC1) to a subset of its target loci. Our results demonstrate a chromatin-associated role of Nup153 in maintaining stem cell pluripotency by functioning in mammalian epigenetic gene silencing.
核孔蛋白（Nups）是一类蛋白质，最为人所知的是作为核孔复合体（NPCs）的组成构建块，核孔复合体是嵌入膜中的通道，介导核运输穿过核膜。最近的证据表明，几种核孔蛋白在控制发育基因的激活和沉默方面具有额外作用；然而，这些功能的机制细节仍知之甚少。在这里，我们表明，小鼠胚胎干细胞（mESCs）中Nup153的缺失会导致发育基因的去抑制和早期分化的诱导。这种干细胞特性的丧失与关键多能性因子的核输入缺陷无关。相反，Nup153结合在发育基因的转录起始位点（TSS）周围，并介导多梳抑制复合体1（PRC1）募集到其一部分靶基因座。我们的结果证明了Nup153在哺乳动物表观遗传基因沉默中发挥作用，从而在维持干细胞多能性方面具有与染色质相关的作用。
