Transcriptional read-through is not sufficient to induce an epigenetic switch in the silencing activity of Polycomb response elements
Transcriptional read-through is not sufficient to induce an epigenetic switch in the silencing activity of Polycomb response elements
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DOI：
10.1073/pnas.1515276112
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发表时间：
2015-12-01
影响因子：
11.1
通讯作者：
Chetverina, Darya
中科院分区：
文献类型：
--
作者：
Erokhin, Maksim;Elizar'ev, Pavel;Chetverina, Darya
在果蝇中，Polycomb（PcG）和TrxG（TrxG）组蛋白组装在Polycomb反应元件（PRE）上，以维持组织和阶段特异性的基因表达模式。对于协调基因表达与分化过程至关重要，PRE的活性可以“打开”和“关闭”。当开启时，PRE对同一结构域中的基因施加沉默状态，该结构域通过多轮细胞分裂稳定遗传。当PRE被关闭时，该结构域处于允许基因表达的状态，可以稳定遗传。以前的研究表明，通过PRE序列的转录突发取代PcG蛋白，并提供了一个通用的机制，诱导PRE活性从开到关的遗传开关;然而，支持这种模型的证据是间接的。在这里，我们直接测试了转录通读机制。与以前的建议相反，我们表明，通过PRE转录是不足以诱导PRE活性的表观遗传开关。事实上，即使通过PRE进行高水平的连续转录，也不能去除PcG蛋白，也不能去除抑制性组蛋白标记。我们的研究结果表明，其他机制，涉及相邻的DNA调控元件必须牵连在遗传开关的PRE活动。
In Drosophila, Polycomb (PcG) and Trithorax (TrxG) group proteins are assembled on Polycomb response elements (PREs) to maintain tissue and stage-specific patterns of gene expression. Critical to coordinating gene expression with the process of differentiation, the activity of PREs can be switched "on" and "off." When on, the PRE imposes a silenced state on the genes in the same domain that is stably inherited through multiple rounds of cell division. When the PRE is switched off, the domain is in a state permissive for gene expression that can be stably inherited. Previous studies have suggested that a burst of transcription through a PRE sequence displaces PcG proteins and provides a universal mechanism for inducing a heritable switch in PRE activity from on to off; however, the evidence favoring this model is indirect. Here, we have directly tested the transcriptional read-through mechanism. Contrary to previous suggestions, we show that transcription through the PRE is not sufficient for inducing an epigenetic switch in PRE activity. In fact, even high levels of continuous transcription through a PRE fails to dislodge the PcG proteins, nor does it remove repressive histone marks. Our results indicate that other mechanisms involving adjacent DNA regulatory elements must be implicated in heritable switch of PRE activity.