High-resolution profiling of Drosophila replication start sites reveals a DNA shape and chromatin signature of metazoan origins.
At every cell cycle, faithful inheritance of metazoan genomes requires the concerted activation of thousands of DNA replication origins. However, the genetic and chromatin features defining metazoan replication start sites remain largely unknown. Here, we delineate the origin repertoire of the Drosophila genome at high resolution. We address the role of origin-proximal G-quadruplexes and suggest that they transiently stall replication forks in vivo. We dissect the chromatin configuration of replication origins and identify a rich spatial organization of chromatin features at initiation sites. DNA shape and chromatin configurations, not strict sequence motifs, mark and predict origins in higher eukaryotes. We further examine the link between transcription and origin firing and reveal that modulation of origin activity across cell types is intimately linked to cell-type-specific transcriptional programs. Our study unravels conserved origin features and provides unique insights into the relationship among DNA topology, chromatin, transcription, and replication initiation across metazoa.
Department of Biosystems Science and Engineering, ETH Zürich, Mattenstrasse 26, 4058 Basel, Switzerland.
Federico
F
Comoglio
Department of Biosystems Science and Engineering, ETH Zürich, Mattenstrasse 26, 4058 Basel, Switzerland.
Tommy
T
Schlumpf
Department of Biosystems Science and Engineering, ETH Zürich, Mattenstrasse 26, 4058 Basel, Switzerland.
Virginia
V
Schmid
Molecular and Computational Biology Program, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
Remo
R
Rohs
Department of Biosystems Science and Engineering, ETH Zürich, Mattenstrasse 26, 4058 Basel, Switzerland.
Christian
C
Beisel
Department of Biosystems Science and Engineering, ETH Zürich, Mattenstrasse 26, 4058 Basel, Switzerland; Faculty of Science, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland. Electronic address: renato.paro@bsse.ethz.ch.
Renato
R
Paro
D000818:Animals; D019540:Area Under Curve; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism*; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004261:DNA Replication; D004330:Drosophila / Q000378:metabolism*; D054856:G-Quadruplexes; D016678:Genome; D006801:Humans; D012372:ROC Curve; D018741:Replication Origin; D024363:Transcription Initiation Site
D002843:Chromatin; D004247:DNA