Heterochromatin-dependent transcription of satellite DNAs in the Drosophila melanogaster female germline

Large blocks of tandemly repeated DNAs—satellite DNAs (satDNAs)—play important roles in heterochromatin formation and chromosome segregation. We know little about how satDNAs are regulated, however their misregulation is associated with genomic instability and human diseases. We use the Drosophila melanogaster germline as a model to study the regulation of satDNA transcription and chromatin. Here we show that complex satDNAs (>100-bp repeat units) are transcribed into long noncoding RNAs and processed into piRNAs (PIWI interacting RNAs). This satDNA piRNA production depends on the Rhino-Deadlock-Cutoff complex and the transcription factor Moonshiner—a previously-described non-canonical pathway that licenses heterochromatin-dependent transcription of dual-strand piRNA clusters. We show that this pathway is important for establishing heterochromatin at satDNAs. Therefore, satDNAs are regulated by piRNAs originating from their own genomic loci.  This novel mechanism of satDNA regulation...

大片段串联重复DNA——卫星DNA（satellite DNAs，satDNAs）——在异染色质形成与染色体分离过程中发挥关键作用。目前学界对卫星DNA的调控机制仍知之甚少，但其调控异常与基因组不稳定性及人类疾病密切相关。本研究以黑腹果蝇（Drosophila melanogaster）生殖系为模型，探究卫星DNA的转录与染色质调控机制。实验结果显示，重复单元长度大于100bp的复杂型卫星DNA可转录为长链非编码RNA，并进一步加工为PIWI互作RNA（piRNAs）。该卫星DNA来源piRNA的生成依赖于Rhino-Deadlock-Cutoff复合物与转录因子Moonshiner——这是此前已被阐明的一条非经典通路，可介导异染色质依赖的双链piRNA簇转录许可。我们证实该通路对于卫星DNA位点的异染色质建立至关重要。由此可见，卫星DNA可通过源自自身基因组位点的piRNA实现调控。这一新颖的卫星DNA调控机制...