Heterochromatin and RNAi are required to establish CENP-A chromatin at centromeres

Heterochromatin is defined by distinct posttranslational modifications on histones, such as methylation of histone H3 at lysine 9 ( H3K9), which allows heterochromatin protein 1 ( HP1)- related chromodomain proteins to bind. Heterochromatin is frequently found near CENP-A chromatin, which is the key determinant of kinetochore assembly. We have discovered that the RNA interference ( RNAi)- directed heterochromatin flanking the central kinetochore domain at fission yeast centromeres is required to promote CENP- A(Cnp1) and kinetochore assembly over the central domain. The H3K9 methyltransferase Clr4 ( Suv39); the ribonuclease Dicer, which cleaves heterochromatic double- stranded RNA to small interfering RNA ( siRNA); Chp1, a component of the RNAi effector complex ( RNA- induced initiation of transcriptional gene silencing; RITS); and Swi6 ( HP1) are required to establish CENP-A(Cnp1) chromatin on naive templates. Once assembled, CENP-A(Cnp1) chromatin is propagated by epigenetic means in the absence of heterochromatin. Thus, another, potentially conserved, role for centromeric RNAi- directed heterochromatin has been identified.