Origin Replication Complex Binding, Nucleosome Depletion Patterns, and a Primary Sequence Motif Can Predict Origins of Replication in a Genome with Epigenetic Centromeres

摘要: ABSTRACT Origins of DNA replication are key genetic elements, yet their identification remains elusive in most organisms. In previous work, we found that centromeres contain origins (ORIs) determined epigenetically the pathogenic yeast Candida albicans. this study, used origin recognition complex (ORC) binding and nucleosome occupancy patterns Saccharomyces cerevisiae Kluyveromyces lactis to train a machine learning algorithm predict position active arm (noncentromeric) C. albicans genome. The model identified bona fide as by presence intermediates on nondenaturing two-dimensional (2D) gels. Importantly, these function at native chromosomal loci also autonomously replicating sequences (ARSs) linear plasmid. A “mini-ARS screen” least one often two ARS regions ≥100 bp within each origin. Furthermore, 15-bp AC-rich consensus motif was associated with predicted conferred autonomous activity mini-ARSs. Thus, while them epigenetic, dependent upon critical features, such site for ORC propensity exclusion. IMPORTANCE machinery is highly conserved, definition exactly what specifies differs different species. Here, utilized computational genomics locations combining sites conserved complex, necessary initiation, together chromatin organization patterns. We exhibited developed plasmid assay delimit fragments function. Additionally, short motif, which enriched origins, required demonstrated new paradigm potential from genome no prior information. work suggests has types origins: “hard-wired” rely specific sequence motifs “epigenetic” centromeric recruited kinetochores sequence-independent manner.