%0 Journal Article
%T Control of replication initiation by the Sum1/Rfm1/Hst1 histone deacetylase
%A Jan M Weber
%A Horst Irlbacher
%A Ann E Ehrenhofer-Murray
%J BMC Molecular Biology
%D 2008
%I BioMed Central
%R 10.1186/1471-2199-9-100
%X In this study, we investigated how Sum1 affected replication initiation. We found that it functioned in initiation as a component of the Sum1/Rfm1/Hst1 complex, implying a role for histone deacetylation in origin activity. We identified several origins in the yeast genome whose activity depended on both Sum1 and Hst1. Importantly, sum1жд or hst1жд caused a significant increase in histone H4 lysine 5 (H4 K5) acetylation levels, but not other H4 acetylation sites, at those origins. Furthermore, mutation of lysines to glutamines in the H4 tail, which imitates the constantly acetylated state, resulted in a reduction of origin activity comparable to that in the absence of Hst1, showing that deacetylation of H4 was important for full initiation capacity of these origins.Taken together, our results demonstrate a role for histone deacetylation in origin activity and reveal a novel aspect of origin regulation by chromatin. These results suggest recruitment of the Sum1/Rfm1/Hst1 complex to a number of yeast origins, where Hst1 deacetylated H4 K5.Genome duplication by DNA replication is fundamental for the propagation of genetic material in all organisms. Eukaryotic chromosomes are replicated from multiple start sites called replication origins that initiate bidirectional DNA replication. Replication initiation at these origins is best understood in the yeast Saccharomyces cerevisiae, where approximately 400 origins are used to replicate the DNA of the 16 chromosomes (reviewed in [1]). The ability of yeast origins to provide initiation and thus autonomous replication to plasmids has allowed the functional dissection of origin elements by measuring plasmid maintenance rates and has coined the term autonomous replicative sequence (ARS).Plasmid maintenance studies have revealed that yeast origins have a modular structure. They all share a so-called ARS consensus sequence (ACS), which is a binding site for the origin recognition complex (ORC), the replication initiator. The six-subu
%U http://www.biomedcentral.com/1471-2199/9/100