title: Unraveling cell type-specific and reprogrammable human replication origin signatures associated with G-quadruplex consensus motifs.
abstract: DNA replication is highly regulated, ensuring faithful inheritance of genetic information through each cell cycle. In metazoans, this process is initiated at many thousands of DNA replication origins whose cell type-specific distribution and usage are poorly understood. We exhaustively mapped the genome-wide location of replication origins in human cells using deep sequencing of short nascent strands and identified ten times more origin positions than we expected; most of these positions were conserved in four different human cell lines. Furthermore, we identified a consensus G-quadruplex-forming DNA motif that can predict the position of DNA replication origins in human cells, accounting for their distribution, usage efficiency and timing. Finally, we discovered a cell type-specific reprogrammable signature of cell identity that was revealed by specific efficiencies of conserved origin positions and not by the selection of cell type-specific subsets of origins.
authors: Laboratory of Plasticity of the Genome and Aging, Functional Genomics Institute, Montpellier, France.
authors: Emilie
authors: E
authors: Besnard
authors: Amélie
authors: A
authors: Babled
authors: Laure
authors: L
authors: Lapasset
authors: Ollivier
authors: O
authors: Milhavet
authors: Hugues
authors: H
authors: Parrinello
authors: Christelle
authors: C
authors: Dantec
authors: Jean-Michel
authors: JM
authors: Marin
authors: Jean-Marc
authors: JM
authors: Lemaitre
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D002874:Chromosome Mapping; D016384:Consensus Sequence; D017931:DNA Primers / Q000235:genetics; D004261:DNA Replication / Q000235:genetics; D054856:G-Quadruplexes; D015894:Genome, Human; D006367:HeLa Cells; D006801:Humans; D059372:Nucleotide Motifs; D018741:Replication Origin / Q000235:genetics*
chemical_list: D017931:DNA Primers