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

Matthew M. Edwards, Ning Wang, Ido Sagi, Shay Kinreich, Nissim Benvenisty, Jeannine Gerhardt, Dieter Egli, Amnon Koren

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)114700
Number of pages1
JournalCell Reports
Volume43
Issue number9
DOIs
StatePublished - 24 Sep 2024

Bibliographical note

Publisher Copyright:
Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

Keywords

  • CP: Genomics
  • CP: Molecular biology
  • DNA replication timing
  • epigenetics
  • genomic imprinting
  • human embryonic stem cells
  • Prader-Willi syndrome

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