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Nuclear pore proteins regulate chromatin structure and transcriptional memory by a conserved mechanism

机译:核孔蛋白通过保守机制调节染色质结构和转录记忆

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摘要

Previous experience alters the rate of transcriptional induction of many genes in yeast, and this phenomenon persists through several cell division cycles. This phenomenon is called epigenetic transcriptional memory. For the yeast gene INO1, transcriptional memory requires a physical interaction with the nuclear pore complex (NPC) and changes in the chromatin structure of the promoter. These changes lead to binding of a preinitiation form of RNA Polymerase II (RNAPII) to the INO1 promoter, bypassing the need to recruit RNAPII to the promoter during reactivation. In our recent study, we found that in human cells, hundreds of interferon-γ responsive genes exhibit a mechanistically similar form of transcriptional memory. Transcriptional memory requires a homologous nuclear pore protein in yeast and humans, which interacts with the promoters of genes that exhibit transcriptional memory and promotes both alteration of chromatin structure and binding of RNAPII. Whereas the interaction of yeast genes with nuclear pore proteins occurs at the NPC, the interaction of human genes with nuclear pore proteins occurs in the nucleoplasm. Thus, the interaction of nuclear pore proteins with genes plays an important and conserved role in affecting long-term epigenetic changes in transcriptional regulation.
机译:先前的经验改变了酵母中许多基因的转录诱导速率,并且这种现象在几个细胞分裂周期中持续存在。这种现象称为表观遗传转录记忆。对于酵母基因INO1,转录记忆需要与核孔复合体(NPC)进行物理相互作用,并需要启动子的染色质结构发生变化。这些变化导致预聚合形式的RNA聚合酶II(RNAPII)与INO1启动子结合,从而避免了在重新激活过程中将RNAPII募集到启动子的需要。在我们最近的研究中,我们发现在人类细胞中,数百种干扰素-γ反应性基因表现出机制上相似的转录记忆形式。转录记忆需要酵母和人类中的同源核孔蛋白,该蛋白与显示转录记忆的基因的启动子相互作用,并促进染色质结构的改变和RNAPII的结合。酵母基因与核孔蛋白的相互作用发生在NPC上,而人类基因与核孔蛋白的相互作用发生在核质中。因此,核孔蛋白与基因的相互作用在影响转录调控的长期表观遗传变化中起着重要且保守的作用。

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