Parent-of-origin-specific DNA replication timing is confined to large imprinted regions.

TitleParent-of-origin-specific DNA replication timing is confined to large imprinted regions.
Publication TypeJournal Article
Year of Publication2024
AuthorsEdwards MM, Wang N, Sagi I, Kinreich S, Benvenisty N, Gerhardt J, Egli D, Koren A
JournalCell Rep
Volume43
Issue9
Pagination114700
Date Published2024 Sep 24
ISSN2211-1247
KeywordsAlleles, Cell Differentiation, DNA Methylation, DNA Replication, DNA Replication Timing, Genomic Imprinting, Human Embryonic Stem Cells, Humans, Multigene Family, Prader-Willi Syndrome
Abstract

Genomic imprinting involves differential DNA methylation and gene expression between homologous paternal and maternal loci. It remains unclear, however, whether DNA replication also shows parent-of-origin-specific patterns at imprinted or other genomic regions. Here, we investigate genome-wide asynchronous DNA replication utilizing uniparental human embryonic stem cells containing either maternal-only (parthenogenetic) or paternal-only (androgenetic) DNA. Four clusters of imprinted genes exhibited differential replication timing based on parent of origin, while the remainder of the genome, 99.82%, showed no significant replication asynchrony between parental origins. Active alleles in imprinted gene clusters replicated earlier than their inactive counterparts. At the Prader-Willi syndrome locus, replication asynchrony spanned virtually the entirety of S phase. Replication asynchrony was carried through differentiation to neuronal precursor cells in a manner consistent with gene expression. This study establishes asynchronous DNA replication as a hallmark of large imprinted gene clusters.

DOI10.1016/j.celrep.2024.114700
Alternate JournalCell Rep
PubMed ID39235941