Integrative analysis of DNA replication origins and ORC-/MCM-binding sites in human cells reveals a lack of overlap

• DOI: 10.7554/elife.89548.4
• Publication Date: 2024-04-03T11:20:41Z
• Authors: Mengxue Tian; Zhenjia Wang; Zhangli Su; Etsuko Shibata; Yoshiyuki Shibata; Anindya Dutta; Chongzhi Zang
• Keywords: CTCF; Origin recognition complex; DNA binding site; Replication timing

Based on experimentally determined average inter-origin distances of ~100 kb, DNA replication initiates from ~50,000 origins human chromosomes in each cell cycle. The are believed to be specified by binding factors like the origin recognition complex (ORC) or CTCF other features G-quadruplexes. We have performed an integrative analysis 113 genome-wide profiles (from five different techniques) and ORC-binding critically evaluate whether most reproducible these features. Out ~7.5 million union identified all datasets, only 0.27% (20,250 shared origins) were reproducibly obtained at least 20 independent SNS-seq datasets contained initiation zones three techniques, suggesting extensive variability usage identification. Also, 21% overlap with transcriptional promoters, posing a conundrum. Although more than constitutive CTCF-binding sites, G-quadruplex activating histone marks, overlaps comparable less that known transcription start so could enriched because epigenetically open, promoter-like sequences. Only 6.4% 20,250 within 1 kb any ~13,000 sites cancer cells, 4.5% ~11,000 MCM2-7-binding contrast nearly 100% two comparisons yeast, Saccharomyces cerevisiae . Thus, lines, appear highly variable stochastic events dependent high epigenetic accessibility around without between currently ORC- MCM-binding sites.