Decision letter: S-phase-independent silencing establishment in Saccharomyces cerevisiae [peer_review]

Tim Formosa, Rohinton T Kamakaka, Danesh Moazed, Kevin Struhl, Tim Formosa
2020 unpublished
The establishment of silent chromatin, a heterochromatin-like structure at HML and HMR in Saccharomyces cerevisiae, depends on progression through S phase of the cell cycle, but the molecular nature of this requirement has remained elusive despite intensive study. Using highresolution chromatin immunoprecipitation and single-molecule RNA analysis, we found that silencing establishment proceeded via gradual repression of transcription in individual cells over several cell cycles, and that the
more » ... es, and that the cell-cycle-regulated step was downstream of Sir protein recruitment. In contrast to prior results, HML and HMR had identical cell-cycle requirements for silencing establishment, with no apparent contribution from a tRNA gene adjacent to HMR. We identified the cause of the S-phase requirement for silencing establishment: removal of transcription-favoring histone modifications deposited by Dot1, Sas2, and Rtt109. These results revealed that silencing establishment was absolutely dependent on the cell-cycle-regulated interplay between euchromatic and heterochromatic histone modifications. Goodnight and Rine. eLife 2020;9:e58910. DOI: https://doi.org/10.7554/eLife.58910 1 of 23 RESEARCH ARTICLE Goodnight and Rine. eLife 2020;9:e58910.
doi:10.7554/elife.58910.sa1 fatcat:fxwl6ygdbfdonc775tvidsvk7q