A conserved role for human Nup98 in altering chromatin structure and promoting epigenetic transcriptional memory.
A conserved role for human Nup98 in altering chromatin structure and promoting epigenetic transcriptional memory.
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DOI：
10.1371/journal.pbio.1001524
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发表时间：
2013
期刊：
影响因子：
9.8
通讯作者：
Brickner JH
中科院分区：
文献类型：
--
作者：
Light WH;Freaney J;Sood V;Thompson A;D'Urso A;Horvath CM;Brickner JH
在酵母和人类中，核孔蛋白与启动子的相互作用改变了染色质结构，并允许RNA聚合酶II结合，使它们更快地重新激活几代。核孔蛋白与活性基因的相互作用可以促进活性基因的转录。在酵母中，一些可诱导的基因与核孔复合物相互作用，无论是在激活时还是在被抑制后的几代，这种现象称为表观遗传转录记忆。这种相互作用促进未来的再激活，并需要Nup 100，人类Nup 98的同源物。类似的现象也发生在人类细胞中;在用干扰素γ（IFN-γ）处理后的至少四代中，许多IFN-γ诱导基因比先前未暴露于IFN-γ的细胞更快、更强地被诱导。在酵母和人类细胞中，最近表达的记忆基因启动子表现出组蛋白H3赖氨酸4（H3 K4 me 2）的持续二甲基化，并与Nups和RNA聚合酶II的平衡形式发生物理相互作用。然而，在人类细胞中，与酵母不同，这些相互作用发生在核质中。在瞬时耗尽Nup 98的人类细胞或缺乏Nup 100的酵母细胞中，转录记忆丢失; RNA聚合酶II不保持与启动子的结合，H3 K4 me 2丢失，并且转录再激活的速率降低。这些结果表明，Nup 100/Nup 98结合最近表达的启动子在促进表观遗传转录记忆中起着保守的作用。细胞通过改变基因的表达来对营养或信号分子的变化做出反应。基因开启的速率并不均匀;有些基因诱导得很快，而另一些基因诱导得很慢。在啤酒酵母中，先前的经验可以提高基因再次启动的速度，这种现象称为“转录记忆”。阻遏后，这些基因与核孔复合物发生物理相互作用，导致染色质结构改变，并与稳定的RNA聚合酶II结合。受干扰素γ诱导的人类基因表现出类似的行为。在这两种情况下，这种现象通过几次细胞分裂持续存在，表明它是表观遗传的。在这里，我们发现酵母和人类细胞利用类似的分子机制来启动基因重新激活。在这两个物种中，核孔蛋白Nup 100/Nup 98与表现出转录记忆的基因的启动子结合。这导致启动子中染色质状态的改变和RNA聚合酶II的结合，使基因为未来的表达而平衡。我们的结论是，单细胞和多细胞生物使用核孔蛋白在一个新的方式来改变转录的基础上以前的经验。
In yeast and humans, interaction of a nuclear pore protein with promoters alters chromatin structure and allows RNA polymerase II to bind, poising them for faster reactivation for several generations. The interaction of nuclear pore proteins (Nups) with active genes can promote their transcription. In yeast, some inducible genes interact with the nuclear pore complex both when active and for several generations after being repressed, a phenomenon called epigenetic transcriptional memory. This interaction promotes future reactivation and requires Nup100, a homologue of human Nup98. A similar phenomenon occurs in human cells; for at least four generations after treatment with interferon gamma (IFN-γ), many IFN-γ-inducible genes are induced more rapidly and more strongly than in cells that have not previously been exposed to IFN-γ. In both yeast and human cells, the recently expressed promoters of genes with memory exhibit persistent dimethylation of histone H3 lysine 4 (H3K4me2) and physically interact with Nups and a poised form of RNA polymerase II. However, in human cells, unlike yeast, these interactions occur in the nucleoplasm. In human cells transiently depleted of Nup98 or yeast cells lacking Nup100, transcriptional memory is lost; RNA polymerase II does not remain associated with promoters, H3K4me2 is lost, and the rate of transcriptional reactivation is reduced. These results suggest that Nup100/Nup98 binding to recently expressed promoters plays a conserved role in promoting epigenetic transcriptional memory. Cells respond to changes in nutrients or signaling molecules by altering the expression of genes. The rate at which genes are turned on is not uniform; some genes are induced rapidly and others are induced slowly. In brewer's yeast, previous experience can enhance the rate at which genes are turned on again, a phenomenon called “transcriptional memory.” After repression, such genes physically interact with the nuclear pore complex, leading to altered chromatin structure and binding of a poised RNA polymerase II. Human genes that are induced by interferon gamma show a similar behavior. In both cases, the phenomenon persists through several cell divisions, suggesting that it is epigenetically inherited. Here, we find that yeast and human cells utilize a similar molecular mechanism to prime genes for reactivation. In both species, the nuclear pore protein Nup100/Nup98 binds to the promoters of genes that exhibit transcriptional memory. This leads to an altered chromatin state in the promoter and binding of RNA polymerase II, poising genes for future expression. We conclude that both unicellular and multicellular organisms use nuclear pore proteins in a novel way to alter transcription based on previous experiences.
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影响因子：
9.8
作者：
Brickner DG;Cajigas I;Fondufe-Mittendorf Y;Ahmed S;Lee PC;Widom J;Brickner JH
通讯作者：
Brickner JH
影响因子：
16
作者：
Esnault, Cyril;Ghavi-Helm, Yad;Werner, Michel
通讯作者：
Werner, Michel
影响因子：
3.3
作者：
Aitchison JD;Rout MP
通讯作者：
Rout MP
影响因子：
5.3
作者：
Enninga, J;Levay, A;Fontoura, BMA
通讯作者：
Fontoura, BMA
影响因子：
32.4
作者：
Faria, AMC;Levay, A;Fontoura, BMA
通讯作者：
Fontoura, BMA