Distinct chromatin regulators downmodulate meiotic axis formation and DNA break induction at chromosome ends
Raghavan, A. R.; May, K.; Subramanian, V. V.; Blitzblau, H. G.; Patel, N. J.; Houseley, J.; Hochwagen, A.
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In many organisms, meiotic crossover recombination is suppressed near the extreme ends of chromosomes. Here we show that multiple, often chromosome-specific, suppressive mechanisms with differing ranges combine to produce the consistently low enrichment of recombination-promoting axis proteins and downregulation of DNA double-strand breaks (DSBs) within 20 kb of telomeres in Saccharomyces cerevisiae. Suppression of axis proteins is associated with cis-encoded signals, including reduced coding density and the subtelomeric Y elements, which are present at many chromosome ends, but also requires chromatin modifiers, including the histone methyltransferase Dot1 and the Sir silencing complex. We show that Dot1 suppresses Sir complex activity at least in part independently of its canonical target, H3K79, to downmodulate axis protein deposition near chromosome ends. In parallel, the Sir complex, but not Dot1, suppresses the induction of DSBs by limiting the openness of promoters, the preferred sites of meiotic DSB formation. The separable downmodulation of axis protein deposition and DSB induction likely contributes to the robust reduction of meiotic recombination effectors near chromosome ends.
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