Genome-wide identification and characterisation of human DNA replication origins by initiation site sequencing (ini-seq)

AbstractGenomic stability depends on faithful genome replication. This is achieved by the concerted activity of thousands of DNA replication origins (ORIs) scattered throughout the genome. In spite of multiple efforts, the DNA and chromatin features that determine ORI specification are not presently known. We have generated a high-resolution genome-wide map of ORIs in cultured Arabidopsis thaliana cells that rendered a collection of 3230 ORIs. In this study we focused on defining the features associated with ORIs in heterochromatin. We found that while ORIs tend to colocalize with genes in euchromatic gene-rich regions, they frequently colocalize with transposable elements (TEs) in pericentromeric gene-poor domains. Interestingly, ORIs in TEs associate almost exclusively with retrotransposons, in particular, of the Gypsy family. ORI activity in retrotransposons occurs independently of TE expression and while maintaining high levels of H3K9me2 and H3K27me1, typical marks of repressed heterochromatin. ORI-TEs largely colocalize with chromatin signatures defining GC-rich heterochromatin. Importantly, TEs with active ORIs contain a local GC content higher than the TEs lacking them. Our results lead us to conclude that ORI colocalization with TEs is largely limited to retrotransposons, which are defined by their transposition mechanisms based on transcription, and they occur in a specific chromatin landscape. Our detailed analysis of ORIs responsible for heterochromatin replication has also implications on the mechanisms of ORI specification in other multicellular organisms in which retrotransposons are major components of heterochromatin as well as of the entire genome.

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Genome-wide mapping of nuclear mitochondrial DNA sequences links DNA replication origins to chromosomal double-strand break formation in Schizosaccharomyces pombe

Genome Research ◽

10.1101/gr.104513.109 ◽

2010 ◽

Vol 20 (9) ◽

pp. 1250-1261 ◽

Cited By ~ 21

Author(s):

S. Lenglez ◽

D. Hermand ◽

A. Decottignies

Keyword(s):

Mitochondrial Dna ◽

Dna Replication ◽

Schizosaccharomyces Pombe ◽

Dna Sequences ◽

Strand Break ◽

Double Strand Break ◽

Replication Origins ◽

Genome Wide ◽

Dna Replication Origins ◽

Break Formation

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Genome-wide mapping of 8-oxo-7,8-dihydro-2′-deoxyguanosine reveals accumulation of oxidatively-generated damage at DNA replication origins within transcribed long genes of mammalian cells

Nucleic Acids Research ◽

10.1093/nar/gky1152 ◽

2018 ◽

Vol 47 (1) ◽

pp. 221-236 ◽

Cited By ~ 24

Author(s):

Stefano Amente ◽

Giacomo Di Palo ◽

Giovanni Scala ◽

Tiziana Castrignanò ◽

Francesca Gorini ◽

...

Keyword(s):

Dna Replication ◽

Mammalian Cells ◽

Replication Origins ◽

Genome Wide ◽

Dna Replication Origins ◽

Long Genes

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