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 language | English |
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Pages (from-to) | 114700 |
Number of pages | 1 |
Journal | Cell Reports |
Volume | 43 |
Issue number | 9 |
DOIs | |
State | Published - 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