Selectivity of ORC binding sites in the human genome and the relation to replication timing, fragile sites, and recurrent deletions in cancers

The origin recognition complex (ORC) binds specific sites in mammalian genomes, from which DNA replication is initiated. Here, we address ORC binding selectivity in vivo by mapping ~52,000 ORC2 binding sites throughout the human genome. The ORC binding profile is broader than that of sequence-specific transcription factors, suggesting that it does not bind to specific DNA sequences. Instead, ORC binds to open (DNase I hypersensitive) regions in which histone H3 tails are hyperacetylated and also di-methylated at lysine 4. Our results suggest that ORC binding selectivity in vivo is determined by a novel mechanism involving non-specific interaction with accessible DNA and recognition of modified histones. ORC sites are far more prevalent in early replicating regions, suggesting that replication timing is primarily due to ORC density and stochastic firing of origins. Large genomic regions lacking ORC2 binding sites are strongly associated with common fragile sites and recurrent deletions in cancers. Overall design: ChIP-seq for ORC2 in K562 cells Please note that the raw data for the ''ORC2 ChIP-seq N-terminus antibody'' sample is lost and thus, only its processed data is provided.