A transcription factor Abf1 facilitates ORC binding onto the Saccharomyces cerevisiae replication origin via histone acetylase Gcn5

Abstract

AbstractChromatin structure has been implicated in the regulation of DNA replication but the molecular mechanism involved is unclear. In this study, we observed that binding of the transcription factor Abf1 to the replication origin ARS1 facilitated the association of the origin recognition complex (ORC) with ARS1 using genetic interaction analysis and ChIP assay. The histone acetyltransferases (HATs), Gcn5 and Esa1, were also loaded onto ARS1 in an Abf1 site-dependent manner, where they were then responsible for acetylating histone H3 lysine 18 (H3K18) and histone H4 lysine 12 (H4K12), respectively. Interestingly, Abf1 interacted with Gcn5, while ORC interacted with Esa1. Indeed the B3 element showed genetic interaction with Gcn5 and Rpd3 not with Esa1, Act3 and Tra1.These data suggest that Gcn5, which is recruited by Abf1, alters chromatin structure via histone acetylation and facilitates the loading of ORC. We therefore propose that transcription factors regulate chromatin structure at replication origins by recruiting chromatin-modifying proteins, such as HATs, to load the initiator.