稳定的可遗传种系沉默在内源基因座指导体细胞沉默。
Stable Heritable Germline Silencing Directs Somatic Silencing at an Endogenous Locus.
作者信息
Minkina Olga, Hunter Craig P
机构信息
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
出版信息
Mol Cell. 2017 Feb 16;65(4):659-670.e5. doi: 10.1016/j.molcel.2017.01.034.
The importance of transgenerationally inherited epigenetic states to organismal fitness remains unknown as well-documented examples are often not amenable to mechanistic analysis or rely on artificial reporter loci. Here we describe an induced silenced state at an endogenous locus that persists, at 100% transmission without selection, for up to 13 generations. This unusually persistent silencing enables a detailed molecular genetic analysis of an inherited epigenetic state. We find that silencing is dependent on germline nuclear RNAi factors and post-transcriptional mechanisms. Consistent with these later observations, inheritance does not require the silenced locus, and we provide genetic evidence that small RNAs embody the inherited silencing signal. Notably, heritable germline silencing directs somatic epigenetic silencing. Somatic silencing does not require somatic nuclear RNAi but instead requires both maternal germline nuclear RNAi and chromatin-modifying activity. Coupling inherited germline silencing to somatic silencing may enable selection for physiologically important traits.
跨代遗传的表观遗传状态对生物体适应性的重要性仍然未知，因为有充分记录的例子往往不适合进行机制分析，或者依赖于人工报告基因座。在这里，我们描述了一个内源性位点的诱导沉默状态，该状态在无选择的情况下以100%的传递率持续存在长达13代。这种异常持久的沉默使得对遗传表观遗传状态进行详细的分子遗传学分析成为可能。我们发现沉默依赖于生殖系核RNAi因子和转录后机制。与这些后来的观察结果一致，遗传不需要沉默位点，并且我们提供了遗传证据表明小RNA体现了遗传沉默信号。值得注意的是，可遗传的生殖系沉默指导体细胞表观遗传沉默。体细胞沉默不需要体细胞核RNAi，而是需要母体生殖系核RNAi和染色质修饰活性。将遗传的生殖系沉默与体细胞沉默相结合可能有助于选择生理上重要的性状。
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