Project description:Some features underlying replication origin activation in metazoan cells have been identified, but little is known about their regulation during metazoan development. Using the nascent strand purification method, we identified replication origins throughout Caenorhabditis elegans embryonic development and found that the origin repertoire is thoroughly reorganized after gastrulation onset. During the pluripotent embryonic stages (pre-gastrula), potential cruciform structures and open chromatin are determinant factors to establish replication origins. The enrichment of replication origins in transcription factor binding sites and their presence inside promoters of highly transcribed genes, particularly operons, argue that transcriptional activity contributes to replication initiation before gastrulation. After the gastrula transition, when differentiation programs are set in the embryos, origins are particularly selected at enhancers, in the vicinity of CGI-like sequences, and non-coding genes. Our findings suggest that origin selection coordinates replication initiation with transcriptional programs during metazoan development.
