Distinct chromatin regulators downmodulate meiotic axis protein deposition and DNA break induction at chromosome ends [RNA-Seq]
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 achieve 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. Overall design: ChIP-seq Analysis: Input and ChIP samples were prepared to assess the binding dynamics of meiotic and nonmeiotic factors. Each bedgraph file represents the results from Input and ChIP samples. To normalize SK1 reads between genotypes, 20% SK288C yeast spike-in controls were included.  mRNA-seq Analysis: RNA-seq was conducted to detect changes in transcription levels during meiosis in wild-type and mutant S. cerevisiae strains.  TrAEL-seq Analysis: Genome-wide DSBs were mapped during meiosis in S. cerevisiae wild-type and mutant strains using TrAEL-seq.