In eukaryotes, repetitive DNA can become silenced de novo, either transcriptionally or post-transcriptionally, by processes independent of strong sequence-specific cues. The mechanistic nature of such processes remains poorly understood. We found that in the fungus Neurospora crassa , de novo initiation of both transcriptional and post-transcriptional silencing was linked to perturbed chromatin, which was produced experimentally by the aberrant activity of transcription factors at the tetO operator array. Transcriptional silencing was mediated by canonical constitutive heterochromatin. On the other hand, post-transcriptional silencing resembled repeat-induced quelling but occurred normally when homologous recombination was inactivated. All silencing of the tetO array was dependent on SAD-6, fungal ortholog of the SWI/SNF chromatin remodeler ATRX (Alpha Thalassemia/Mental Retardation Syndrome X-Linked), which was required to maintain nucleosome occupancy at the perturbed locus. In addition, we found that two other types of sequences (the lacO array and native AT-rich DNA) could also undergo recombination-independent quelling associated with perturbed chromatin. These results suggested a model in which the de novo initiation of transcriptional and post-transcriptional silencing is coupled to the remodeling of perturbed chromatin.

中文翻译：

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受干扰染色质的重塑可以启动从头转录和转录后沉默


在真核生物中，重复的 DNA 可以通过独立于强序列特异性线索的过程在转录或转录后从头沉默。这种过程的机械性质仍然知之甚少。我们发现在真菌中粗糙脉孢菌，转录和转录后沉默的从头启动与染色质扰动有关，染色质是由转录因子在实验上的异常活性产生的。四环素运算符数组。转录沉默是由典型的组成型异染色质介导的。另一方面，转录后沉默类似于重复诱导的抑制，但在同源重组失活时正常发生。所有的沉默四环素阵列依赖于 SWI/SNF 染色质重塑剂 ATRX（X 连锁阿尔法地中海贫血/智力迟钝综合征）的真菌直系同源物 SAD-6，它是维持扰动位点处核小体占据所必需的。此外，我们发现另外两种类型的序列（乳酸阵列和天然富含 AT 的 DNA）也可能经历与染色质扰动相关的不依赖于重组的抑制。这些结果提出了一个模型，其中转录和转录后沉默的从头启动与受干扰的染色质的重塑相结合。