Genome-scale analysis of metazoan replication origins reveals their organization in specific but flexible sites defined by conserved features

• DOI: 10.1101/gr.121830.111
• Publication Date: 2011-07-13T04:59:43Z
• Authors: Christelle Cayrou; Philippe Coulombe; Alice Vigneron; Slavica Stanojcic; Olivier Ganier; Isabelle Peiffer; Eric Rivals; Aurore Puy; Sabine Laurent-Ch...; Romain Desprat; Marcel Méchali
• Keywords: Genomic Organization; Replication timing; CpG site; Polytene chromosome

In metazoans, thousands of DNA replication origins (Oris) are activated at each cell cycle. Their genomic organization and their genetic nature remain elusive. Here, we characterized Oris by nascent strand (NS) purification a genome-wide analysis in Drosophila mouse cells. We show that both species most CpG islands (CGI) contain Oris, although methylation is nearly absent , indicating this epigenetic mark not crucial for defining the origin. Initiation synthesis starts borders CGI, resulting striking bimodal distribution NS, suggestive dual initiation event. unique nucleotide skew around NS peaks, G/T C/A overrepresentation 5′ 3′ Ori sites, respectively. Repeated GC-rich elements were detected, which good predictors suggesting common sequence features part metazoan Oris. heterochromatic chromosome 4 correlated with HP1 binding sites. At level, regions rich early replicating, whereas Ori-poor late replicating. The was coupled combing to unravel results indicate large excess, but activation does occur random. They organized groups site-specific flexible define replicons, where single origin replicon. This provides site specificity firing flexibility replicon, allowing possible adaptation environmental cues fates.