title: Chromatin signatures of the Drosophila replication program.
abstract: DNA replication initiates from thousands of start sites throughout the Drosophila genome and must be coordinated with other ongoing nuclear processes such as transcription to ensure genetic and epigenetic inheritance. Considerable progress has been made toward understanding how chromatin modifications regulate the transcription program; in contrast, we know relatively little about the role of the chromatin landscape in defining how start sites of DNA replication are selected and regulated. Here, we describe the Drosophila replication program in the context of the chromatin and transcription landscape for multiple cell lines using data generated by the modENCODE consortium. We find that while the cell lines exhibit similar replication programs, there are numerous cell line-specific differences that correlate with changes in the chromatin architecture. We identify chromatin features that are associated with replication timing, early origin usage, and ORC binding. Primary sequence, activating chromatin marks, and DNA-binding proteins (including chromatin remodelers) contribute in an additive manner to specify ORC-binding sites. We also generate accurate and predictive models from the chromatin data to describe origin usage and strength between cell lines. Multiple activating chromatin modifications contribute to the function and relative strength of replication origins, suggesting that the chromatin environment does not regulate origins of replication as a simple binary switch, but rather acts as a tunable rheostat to regulate replication initiation events.
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Eaton
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Prinz
authors.forename: Heather K
authors.initials: HK
authors.lastname: MacAlpine
authors.forename: George
authors.initials: G
authors.lastname: Tretyakov
authors.forename: Peter V
authors.initials: PV
authors.lastname: Kharchenko
authors.forename: David M
authors.initials: DM
authors.lastname: MacAlpine
mesh_terms: D000818:Animals; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D016000:Cluster Analysis; D019295:Computational Biology; D003198:Computer Simulation; D004261:DNA Replication; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D051738:Origin Recognition Complex / Q000235:genetics / Q000378:metabolism; D018741:Replication Origin
chemical_list: D002843:Chromatin; D051738:Origin Recognition Complex