Dynamic changes in chromatin structure through post-translational modifications of histone H3 during replication origin activation.

Genome duplication relies on the timely activation of multiple replication origins throughout the genome during S phase. Each origin is marked by the assembly of a multiprotein pre-replication complex (pre-RC) and the recruitment of the replicative machinery, which can gain access to replication origins on the DNA through the barrier of specific chromatin structures. Inheritance of the genetic information is further accompanied by maintenance and inheritance of the epigenetic marks, which are accomplished by the activity of histone and DNA modifying enzymes traveling with the replisome. Here, we studied the changes in the chromatin structure at the loci of three replication origins, the early activated human lamin B2 (LB2) and monkey Ors8 (mOrs8) origins and the late-activated human homologue of the latter (hOrs8), during their activation, by measuring the abundance of post-translationally modified histone H3. The data show that dynamic changes in the levels of acetylated, methylated and phosphorylated histone H3 occur during the initiation of DNA replication at these three origin loci, which differ between early- and late-firing origins as well as between human- and monkey-derived cell lines. These results suggest that specific histone modifications are associated with origin firing, temporal activation and replication fork progression and underscore the importance of species specificity. (c) 2009 Wiley-Liss, Inc.