Erokhin Maksim, Elizar'ev Pavel, Parshikov Aleksander, Schedl Paul, Georgiev Pavel, Chetverina Darya
Institute of Gene Biology, Russian Academy of Sciences, Moscow 119334, Russia;
Institute of Gene Biology, Russian Academy of Sciences, Moscow 119334, Russia; Department of Molecular Biology, Princeton University, Princeton, NJ 08544.
Proc Natl Acad Sci U S A. 2015 Dec 1;112(48):14930-5. doi: 10.1073/pnas.1515276112. Epub 2015 Oct 26.
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.
在果蝇中，多梳（PcG）蛋白家族和三胸（TrxG）蛋白家族组装在多梳反应元件（PREs）上，以维持基因表达的组织和阶段特异性模式。PREs的活性对于协调基因表达与分化过程至关重要，其活性可以被“开启”和“关闭”。开启时，PRE会使同一结构域中的基因处于沉默状态，这种状态可通过多轮细胞分裂稳定遗传。当PRE关闭时，该结构域处于允许基因表达的状态，且这种状态也可稳定遗传。先前的研究表明，通过PRE序列的转录爆发会取代PcG蛋白，并提供一种将PRE活性从开启状态诱导为关闭状态的可遗传转换的通用机制；然而，支持该模型的证据是间接的。在此，我们直接测试了转录通读机制。与先前的观点相反，我们发现通过PRE的转录不足以诱导PRE活性的表观遗传转换。事实上，即使通过PRE进行高水平的持续转录，也无法去除PcG蛋白，也不会消除抑制性组蛋白标记。我们的结果表明，涉及相邻DNA调控元件的其他机制必定与PRE活性的可遗传转换有关。
