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

Cell Rep. 2024 Sep 24;43(9):114700. doi: 10.1016/j.celrep.2024.114700. Epub 2024 Sep 4.

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.

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Cell Differentiation / genetics
  • DNA Methylation / genetics
  • DNA Replication / genetics
  • DNA Replication Timing*
  • Genomic Imprinting*
  • Human Embryonic Stem Cells / metabolism
  • Humans
  • Multigene Family
  • Prader-Willi Syndrome / genetics