Interaction of the HAT complex SAS-I with chromatin assembly factors in S. cerevisiae

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Chromatin duplication entails not only copying of the DNA sequence, but also duplicating the chromatin structure. Foremost, histone modification patterns need to be reestablished on the freshly replicated chromatin, since they play a crucial role in determining whether the chromatin is active (euchromatin) or inactive (heterochromatin), which they achieve by controlling the binding of other factors to chromatin. In this proposal, we will submit models for the reestablishment of a euchromatic acetylation mark in S. cerevisiae, the acetylation of H4 K16, to critical tests. Global H4 K16 acetylation is performed by the SAS-I histone acetyltransferase complex. Based on our finding that SAS-I interacts with chromatin assembly factors, we will test the hypothesis that they direct the SAS-I activity to certain genomic regions. Furthermore, we will determine whether SAS-I acetylation occurs before or after histone deposition, and we will molecularly dissect the interaction between SAS-I and the chromatin assembly factors. Finally, we will chart genome-wide SAS-I dependent acetylation. These studies will give important mechanistic insights into how cells ensure that the offspring is epigenetically identical to the parental cells.