The nuclear-envelope protein and transcriptional repressor LAP2β interacts with HDAC3 at the nuclear periphery, and induces histone H4 deacetylation
The nuclear-envelope protein and transcriptional repressor LAP2β interacts with HDAC3 at the nuclear periphery, and induces histone H4 deacetylation
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核膜蛋白和转录抑制因子 LAP2β 与核外围的 HDAC3 相互作用，诱导组蛋白 H4 脱乙酰化
DOI：
10.1242/jcs.02521
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发表时间：
2005
影响因子：
4
通讯作者：
E. Gal
中科院分区：
文献类型：
--
作者：
R. Somech;S. Shaklai;O. Geller;N. Amariglio;A. Simon;G. Rechavi;E. Gal
核膜蛋白与多种基本细胞功能有关，其中包括转录调节。已知核外围区域的基因表达受到组蛋白脱乙酰化和甲基化等表观遗传修饰的抑制。然而，核膜蛋白参与此类修饰的机制仍不清楚。我们之前已经证明，LAP2β是一种完整的核膜蛋白，含有染色质结合LEM结构域，能够抑制E2F5-DP3异二聚体的转录活性。在这里，我们表明 LAP2β 的抑制活性更为普遍，涵盖各种 E2F 成员以及其他转录因子，例如 p53 和 NF-κB。我们进一步表明，LAP2β 在核膜上与 HDAC3（一种 I 类组蛋白脱乙酰酶）相互作用，并且 TSA（一种 HDAC 抑制剂）消除了 LAP2β 的抑制活性。最后，我们证明 LAP2β 能够诱导组蛋白 H4 脱乙酰化。我们的数据提供了证据，证明核外围存在一种以前未知的抑制复合物，该复合物由完整的核膜蛋白和组蛋白修饰剂组成。
Nuclear-envelope proteins have been implicated in diverse and fundamental cell functions, among them transcriptional regulation. Gene expression at the territory of the nuclear periphery is known to be repressed by epigenetic modifications such as histone deacetylation and methylation. However, the mechanism by which nuclear-envelope proteins are involved in such modifications is still obscure. We have previously shown that LAP2β, an integral nuclear-envelope protein that contains the chromatin-binding LEM domain, was able to repress the transcriptional activity of the E2F5-DP3 heterodimer. Here, we show that LAP2β's repressive activity is more general, encompassing various E2F members as well as other transcription factors such as p53 and NF-κB. We further show that LAP2β interacts at the nuclear envelope with HDAC3, a class-I histone deacetylase, and that TSA (an HDAC inhibitor) abrogates LAP2β's repressive activity. Finally, we show that LAP2β is capable of inducing histone-H4 deacetylation. Our data provide evidence for the existence of a previously unknown repressive complex, composed of an integral nuclear membrane protein and a histone modifier, at the nuclear periphery.
影响因子：
7
作者：
Berger, R;Theodor, L;Simon, AJ
通讯作者：
Simon, AJ
DOI：
10.1006/bbrc.1997.8033
发表时间：
1998-01-26
影响因子：
3.1
作者：
Dangond, F;Hafler, DA;Gullans, SR
通讯作者：
Gullans, SR