Establishment of global histone acetylation patterns by the HAT complex SAS-I in S. cerevisiae

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Eukaryotic organisms require sophisticated mechanisms to ensure that gene expression in their ge-nome is carried out in the correct temporal and spatial manner. Posttranslational histone modifications are one mechanism by which gene expression is controlled. Among these, acetylation of H4 lysine 16 (H4 K16Ac) plays an important role in maintaining euchromatic identity. In the previous grant period, we have investigated global H4 K16Ac deposition by the histone acetyltransferase complex SAS-I in Saccharomyces cerevisiae, which lead us to identify unanticipated roles for SAS-I in transcription elongation and the suppression of cryptic initiation within ORFs. In this proposal, we will continue this work and will define the mechanism of H4 K16Ac deposition by SAS-I. We will determine how it is connected to replication- and transcription-dependent and -independent histone deposition. Furthermore, we will determine how the chromatin assembly factors CAF-I and Asf1 contribute to steady-state H4 K16Ac levels as well as how they influence dynamic SAS-I-dependent H4 K16Ac inside and outside of S-phase. These studies are important in order to learn how SAS-I acetylation is directed to certain genomic regions and provide novel insights into the mechanisms that eukaryotes use to establish chromatin domains within their genome.