Heterochromatin and RNAi Are Required to Establish CENP-A Chromatin at Centromeres

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Science  04 Jan 2008:
Vol. 319, Issue 5859, pp. 94-97
DOI: 10.1126/science.1150944

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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-ACnp1 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-ACnp1 chromatin on naïve templates. Once assembled, CENP-ACnp1 chromatin is propagated by epigenetic means in the absence of heterochromatin. Thus, another, potentially conserved, role for centromeric RNAi-directed heterochromatin has been identified.

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