TY - JOUR T1 - Active transcription regulates ORC/MCM distribution whereas replication timing correlates with ORC density in human cells JF - bioRxiv DO - 10.1101/778423 SP - 778423 AU - Nina Kirstein AU - Alexander Buschle AU - Xia Wu AU - Stefan Krebs AU - Helmut Blum AU - Wolfgang Hammerschmidt AU - Olivier Hyrien AU - Benjamin Audit AU - Aloys Schepers Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/09/23/778423.abstract N2 - Eukaryotic replication initiates during S phase from origins that have been licensed in the preceding G1 phase. Here, we compare ChIP-seq profiles of the licensing factors Orc2, Orc3, Mcm3, and Mcm7 with replication initiation events obtained by Okazaki fragment sequencing. We demonstrate that MCM is displaced from early replicating, actively transcribed gene bodies, while ORC is mainly enriched at active TSS. Late replicating, H4K20me3 containing initiation zones display enhanced ORC and MCM levels. Furthermore, we find early RTDs being primarily enriched in ORC, compared to MCM, indicating that ORC levels are involved in organizing the temporal order of DNA replication. The organizational connection between active transcription and replication competence directly links changes in the transcriptional program to flexible replication patterns, which ensures the cell’s flexibility to respond to environmental cues. ER -