Akerman, Ildem ORCID: 0000-0002-9875-1421, Kasaai, Bahar, Bazarova, Alina, Sang, Pau Biak, Peiffer, Isabelle, Artufel, Marie, Derelle, Romain, Smith, Gabrielle, Rodriguez-Martinez, Marta, Romano, Manuela, Kinet, Sandrina, Tino, Peter, Theillet, Charles, Taylor, Naomi, Ballester, Benoit ORCID: 0000-0002-0834-7135 and Mechali, Marcel (2020). A predictable conserved DNA base composition signature defines human core DNA replication origins. Nat. Commun., 11 (1). BERLIN: NATURE RESEARCH. ISSN 2041-1723

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Abstract

DNA replication initiates from multiple genomic locations called replication origins. In metazoa, DNA sequence elements involved in origin specification remain elusive. Here, we examine pluripotent, primary, differentiating, and immortalized human cells, and demonstrate that a class of origins, termed core origins, is shared by different cell types and host similar to 80% of all DNA replication initiation events in any cell population. We detect a shared G-rich DNA sequence signature that coincides with most core origins in both human and mouse genomes. Transcription and G-rich elements can independently associate with replication origin activity. Computational algorithms show that core origins can be predicted, based solely on DNA sequence patterns but not on consensus motifs. Our results demonstrate that, despite an attributed stochasticity, core origins are chosen from a limited pool of genomic regions. Immortalization through oncogenic gene expression, but not normal cellular differentiation, results in increased stochastic firing from heterochromatin and decreased origin density at TAD borders.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Akerman, IldemUNSPECIFIEDorcid.org/0000-0002-9875-1421UNSPECIFIED
Kasaai, BaharUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bazarova, AlinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sang, Pau BiakUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peiffer, IsabelleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Artufel, MarieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Derelle, RomainUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Smith, GabrielleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rodriguez-Martinez, MartaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Romano, ManuelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kinet, SandrinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tino, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Theillet, CharlesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Taylor, NaomiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ballester, BenoitUNSPECIFIEDorcid.org/0000-0002-0834-7135UNSPECIFIED
Mechali, MarcelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-318671
DOI: 10.1038/s41467-020-18527-0
Journal or Publication Title: Nat. Commun.
Volume: 11
Number: 1
Date: 2020
Publisher: NATURE RESEARCH
Place of Publication: BERLIN
ISSN: 2041-1723
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ORC-BINDING-SITES; GENOME-WIDE; INITIATION; IDENTIFICATION; TRANSCRIPTION; REVEALS; COMPLEX; DOMAINS; GENE; ORGANIZATIONMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/31867

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