The INO80 complex regulates epigenetic inheritance of heterochromatin (RNA-seq)

One key aspect of epigenetic inheritance is that chromatin structure can be stably inherited through generations even after removal of the initial signal that establishes such structure. In fission yeast, the RNA interference (RNAi) machinery is critical for the targeting of histone methyltransferase Clr4 to repetitive DNA elements to establish a large domain of heterochromatin marked with histone H3 lysine 9 methylation (H3K9me). Subsequently during DNA replication, the deposition of parental histones containing H3K9me into daughter DNA strands is expected to recruit Clr4 to modify neighboring new histones, resulting in the inheritance of heterochromatin in both daughter cells. However, pericentric heterochromatin cannot be properly inherited in the absence of RNAi, suggesting the existence of mechanisms that counteract chromatin-based inheritance. Here we show that in the absence of certain components of the INO80 chromatin remodeling complex, pericentric heterochromatin can be properly inherited in RNAi mutants. The ability of INO80 to counter heterochromatin inheritance is attributed to one accessory subunit Iec5, which promotes histone turn over at heterochromatin regions, but has little effects on the ability of INO80 in regulating nucleosome positioning at heterochromatin, gene expression, or the DNA damage response. Slow histone turnover preserves parental histones at repeat regions to enhance epigenetic inheritance of heterochromatin not only in RNAi mutants but also in wild type cells. Our analyses identified a separation-of-function mutation of INO80 in regulating histone turnover at heterochromatin and demonstrate the important role of histone turnover in controlling heterochromatin inheritance and maintaining the proper heterochromatin landscape of the genome. Overall design: RNA-seq analysis of three ino80 mutants