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High-resolution profiling of Drosophila replication start sites reveals a DNA shape and chromatin signature of metazoan origins.

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Publication date 2015
Author Comoglio Federico, Schlumpf Tommy, Schmid Virginia, Rohs Remo, Beisel Christian, Paro Renato,
Project Mechanisms of transcriptional memory in response to developmental and environmental stimuli
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Original article (peer-reviewed)

Journal Cell reports
Volume (Issue) 11(5)
Page(s) 821 - 34
Title of proceedings Cell reports
DOI 10.1016/j.celrep.2015.03.070

Open Access

URL http://dx.doi.org/10.1016/j.celrep.2015.03.070
Type of Open Access Publisher (Gold Open Access)

Abstract

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.
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