Title | Parent-of-origin-specific DNA replication timing is confined to large imprinted regions. |
Publication Type | Journal Article |
Year of Publication | 2024 |
Authors | Edwards MM, Wang N, Sagi I, Kinreich S, Benvenisty N, Gerhardt J, Egli D, Koren A |
Journal | Cell Rep |
Volume | 43 |
Issue | 9 |
Pagination | 114700 |
Date Published | 2024 Sep 24 |
ISSN | 2211-1247 |
Keywords | Alleles, 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. |
DOI | 10.1016/j.celrep.2024.114700 |
Alternate Journal | Cell Rep |
PubMed ID | 39235941 |