title: DNA replication-timing analysis of human chromosome 22 at high resolution and different developmental states.
abstract: Duplication of the genome during the S phase of the cell cycle does not occur simultaneously; rather, different sequences are replicated at different times. The replication timing of specific sequences can change during development; however, the determinants of this dynamic process are poorly understood. To gain insights into the contribution of developmental state, genomic sequence, and transcriptional activity to replication timing, we investigated the timing of DNA replication at high resolution along an entire human chromosome (chromosome 22) in two different cell types. The pattern of replication timing was correlated with respect to annotated genes, gene expression, novel transcribed regions of unknown function, sequence composition, and cytological features. We observed that chromosome 22 contains regions of early- and late-replicating domains of 100 kb to 2 Mb, many (but not all) of which are associated with previously described chromosomal bands. In both cell types, expressed sequences are replicated earlier than nontranscribed regions. However, several highly transcribed regions replicate late. Overall, the DNA replication-timing profiles of the two different cell types are remarkably similar, with only nine regions of difference observed. In one case, this difference reflects the differential expression of an annotated gene that resides in this region. Novel transcribed regions with low coding potential exhibit a strong propensity for early DNA replication. Although the cellular function of such transcripts is poorly understood, our results suggest that their activity is linked to the replication-timing program.
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520-8103, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: White
authors.forename: Olof
authors.initials: O
authors.lastname: Emanuelsson
authors.forename: David
authors.initials: D
authors.lastname: Scalzo
authors.forename: Thomas
authors.initials: T
authors.lastname: Royce
authors.forename: Steven
authors.initials: S
authors.lastname: Kosak
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Oakeley
authors.forename: Sherman
authors.initials: S
authors.lastname: Weissman
authors.forename: Mark
authors.initials: M
authors.lastname: Gerstein
authors.forename: Mark
authors.initials: M
authors.lastname: Groudine
authors.forename: Michael
authors.initials: M
authors.lastname: Snyder
authors.forename: Dirk
authors.initials: D
authors.lastname: Schübeler
mesh_terms: D002454:Cell Differentiation; D002460:Cell Line; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics* / Q000378:metabolism*; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D042522:DNA Replication Timing; D020869:Gene Expression Profiling; D006801:Humans; D007621:Karyotyping; D008168:Lung / Q000166:cytology / Q000378:metabolism; D009928:Organ Specificity; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013997:Time Factors; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D004247:DNA