The Ino80 complex mediates epigenetic centromere propagation via active removal of histone H3

The centromere is the chromosomal locus at which the kinetochore is assembled to direct chromosome segregation. The histone H3 variant, centromere protein A (CENP-A), is known to epigenetically mark active centromeres, but the mechanism by which CENP-A propagates at the centromere, replacing histone H3, remains poorly understood. Using fission yeast, here we show that the Ino80 adenosine triphosphate (ATP)-dependent chromatin-remodeling complex, which removes histone H3-containing nucleosomes from associated chromatin, promotes CENP-A(Cnp1) chromatin assembly at the centromere in a redundant manner with another chromatin-remodeling factor Chd1(Hrp1). CENP-A(Cnp1) chromatin actively recruits the Ino80 complex to centromeres to elicit eviction of histone H3-containing nucleosomes. Artificial targeting of Ino80 subunits to a non-centromeric DNA sequence placed in a native centromere enhances the spreading of CENP-A(Cnp1) chromatin into the non-centromeric DNA. Based on these results, we propose that CENP-A(Cnp1) chromatin employs the Ino80 complex to mediate the replacement of histone H3 with CENP-A(Cnp1), and thereby reinforces itself.