The JmjC domain protein Epe1 prevents unregulated assembly and disassembly of heterochromatin.
The JmjC domain protein Epe1 prevents unregulated assembly and disassembly of heterochromatin.
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DOI：
10.1038/sj.emboj.7601892
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发表时间：
2007-11-14
期刊：
影响因子：
11.4
通讯作者：
Allshire, Robin C.
中科院分区：
文献类型：
--
作者：
Trewick, Sarah C.;Minc, Elsa;Antonelli, Richard;Urano, Takeshi;Allshire, Robin C.
异染色质通常具有规定的染色体位置，并且不得侵犯邻近区域。我们证明裂殖酵母蛋白 Epe1 可以稳定沉默染色质，防止异染色质结构域的振荡。 Epe1缺失导致两种截然不同的表型：异染色质内沉默的减轻和沉默染色质扩展到邻近常染色质中。因此，我们提出Epe1调节异染色质组装和分解，从而影响异染色质完整性、着丝粒功能和染色体分离保真度。 Epe1 在染色质水平上调节异染色质结构域的范围，而不是通过 RNAi 途径。对异位沉默位点的分析表明，异染色质振荡发生在没有异染色质边界的情况下。 Epe1 需要预测的铁和 2-羟基戊二酸 (2-OG) 结合残基才能发挥体内功能，表明它可能是一种 2-OG/Fe(II) 依赖性双加氧酶。我们认为，Epe1 可能不是组蛋白去甲基化酶，而是一种蛋白质羟化酶，它会影响异染色质蛋白的稳定性或蛋白质-蛋白质相互作用，从而调节异染色质结构域的范围。因此，Epe1 确保异染色质被限制在 RNAi 靶向的区域内。
Heterochromatin normally has prescribed chromosomal positions and must not encroach on adjacent regions. We demonstrate that the fission yeast protein Epe1 stabilises silent chromatin, preventing the oscillation of heterochromatin domains. Epe1 loss leads to two contrasting phenotypes: alleviation of silencing within heterochromatin and expansion of silent chromatin into neighbouring euchromatin. Thus, we propose that Epe1 regulates heterochromatin assembly and disassembly, thereby affecting heterochromatin integrity, centromere function and chromosome segregation fidelity. Epe1 regulates the extent of heterochromatin domains at the level of chromatin, not via the RNAi pathway. Analysis of an ectopically silenced site suggests that heterochromatin oscillation occurs in the absence of heterochromatin boundaries. Epe1 requires predicted iron- and 2-oxyglutarate (2-OG)-binding residues for in vivo function, indicating that it is probably a 2-OG/Fe(II)-dependent dioxygenase. We suggest that, rather than being a histone demethylase, Epe1 may be a protein hydroxylase that affects the stability of a heterochromatin protein, or protein–protein interaction, to regulate the extent of heterochromatin domains. Thus, Epe1 ensures that heterochromatin is restricted to the domains to which it is targeted by RNAi.
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影响因子：
56.9
作者：
Nakayam, J;Rice, JC;Grewal, SIS
通讯作者：
Grewal, SIS
影响因子：
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作者：
Noma, K;Sugiyama, T;Grewal, SIS
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Grewal, SIS
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Jia, ST;Noma, K;Grewal, SIS
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Grewal, SIS
影响因子：
64.5
作者：
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通讯作者：
Grewal, Shiv I. S.
影响因子：
56.9
作者：
Noma, K;Allis, CD;Grewal, SIS
通讯作者：
Grewal, SIS