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作 者:Juan Du Junzheng Zhang Tao He Yajuan Li Ying Su Feng Tie Min Liu Peter J.Harte 朱健
机构地区:[1]不详 [2]北京大学生命科学学院
出 处:《科学新闻》2017年第4期108-108,共1页Science News
基 金:科技部973计划;国家自然科学基金等项目的资助
摘 要:多梳蛋白复合体通过在表观遗传层面抑制发育相关基因的表达,从而确保发育程序的时空次序性调控。目前表观遗传学研究大多集中于探究下游靶基因和组蛋白修饰,但是多梳蛋白自身的活性以及多梳蛋白复合体的稳态如何被调控尚不清楚。Polycomb-group (PcG) proteins function to ensure correct deployment of developmental programs by epigenetically repressing target gene expression. Despite the importance, few studies have been focused on the regulation of PcG activity itself. Here, we report a Drosophila gene, stuxnet (stx), that controls Pc protein stability. We find that heightened stx activity leads to homeotic transformation, reduced Pc activity, and de-repression of PcG targets. Conversely, stx mutants, which can be rescued by decreased Pc expression, display developmental defects resembling hyperactivation of Pc. Our biochemical analyses provide a mechanistic basis for the interaction between stx and Pc; Stx facilitates Pc degradation in the proteasome, independent of ubiquitin modification. Furthermore, this mode of regulation is conserved in vertebrates. Mouse stx promotes degradation of Cbx4, an orthologous Pc protein, in vertebrate cells and induces homeotic transformation in Drosophila. Our results highlight an evolutionarily conserved mechanism of regulated protein degradation on PcG homeostasis and epigenetic activity.
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