Regulation of an inducible promoter by an HP1β-HP1γ switch

Regulation of an inducible promoter by an HP1β-HP1γ switch
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DOI:
10.1038/embor.2008.1
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发表时间:
2008-03-01
期刊:
影响因子:
7.7
通讯作者:
Muchardt, Christian
Muchardt, Christian
中科院分区:
生物学2区
文献类型:
--
作者:
Mateescu, Bogdan;Bourachot, Brigitte;Muchardt, Christian

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最近显示哺乳动物异染色质蛋白 1 (HP1) 家族蛋白参与诱导型启动子的瞬时抑制。其中一个启动子是 HIV1 长末端重复序列,在病毒潜伏期,它会招募非进行性 RNA 聚合酶 II (RNAPII),合成一个短的调节转录本。在这里,我们使用该启动子来检查 HP1 α、HP1 β 和 HP1 γ 与 RNAPII 的相互作用。我们发现,在没有刺激的情况下,HP1b 与非进行性 RNAPII 一起存在于启动子上,并充当负调节因子。激活后,与甲基化 H3K9 结合的 HP1b 在组蛋白 H3 磷酸乙酰化的同时迅速释放,并被 HP1 gamma 取代。该亚型定位于启动子,但也定位于编码区内部,与进行性 RNAPII 一起。我们的数据表明 HP1 招募-释放是一种受到精确调控且高度依赖于转录的顺序机制。
The mammalian heterochromatin protein 1 (HP1) family of proteins was recently shown to be involved in transient repression of inducible promoters. One of these promoters is the HIV1 long terminal repeat, which, during viral latency, recruits a non-processive RNA polymerase II (RNAPII) that synthesizes a short regulatory transcript. Here, we have used this promoter to examine the interplay of HP1 alpha, HP1 beta and HP1 gamma with RNAPII. We find that, in the absence of stimulation, HP1b is present on the promoter together with the non-processive RNAPII and functions as a negative regulator. On activation, HP1b bound to methylated H3K9 is rapidly released concurrent with histone H3 phospho-acetylation, and is replaced by HP1 gamma. This isoform localizes to the promoter but also inside the coding region, together with the processive RNAPII. Our data show that HP1 recruitment-release is a sequential mechanism that is precisely regulated and highly dependent on transcription.