Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Cell Rep. 2020 Dec 29;33(13):108561. doi: 10.1016/j.celrep.2020.108561.
One key aspect of epigenetic inheritance is that chromatin structures can be stably inherited through generations after the removal of the signals that establish such structures. In fission yeast, the RNA interference (RNAi) pathway is critical for the targeting of histone methyltransferase Clr4 to pericentric repeats to establish heterochromatin. However, pericentric heterochromatin cannot be properly inherited in the absence of RNAi, suggesting the existence of mechanisms that counteract chromatin structure inheritance. Here, we show that mutations of components of the INO80 chromatin-remodeling complex allow pericentric heterochromatin inheritance in RNAi mutants. The ability of INO80 to counter heterochromatin inheritance is attributed to one subunit, Iec5, which promotes histone turnover at heterochromatin but has little effects on nucleosome positioning at heterochromatin, gene expression, or the DNA damage response. These analyses demonstrate the importance of the INO80 chromatin-remodeling complex in controlling heterochromatin inheritance and maintaining the proper heterochromatin landscape of the genome.
表观遗传继承的一个关键方面是，染色质结构可以在去除建立这种结构的信号后，通过几代人的稳定遗传。在裂殖酵母中，RNA 干扰（RNAi）途径对于将组蛋白甲基转移酶 Clr4 靶向到着丝粒重复序列以建立异染色质至关重要。然而，如果没有 RNAi，着丝粒异染色质就不能正确遗传，这表明存在抵消染色质结构遗传的机制。在这里，我们表明 INO80 染色质重塑复合物的成分突变允许在 RNAi 突变体中进行着丝粒异染色质遗传。INO80 对抗异染色质遗传的能力归因于一个亚基 Iec5，它促进异染色质上的组蛋白周转，但对异染色质上核小体定位、基因表达或 DNA 损伤反应几乎没有影响。这些分析表明 INO80 染色质重塑复合物在控制异染色质遗传和维持基因组适当的异染色质景观方面的重要性。
