Observational studyNature communications2021
The genetic architecture of DNA replication timing in human pluripotent stem cells.
Observational study in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 36 citations in OpenAlex.
- Article
- Mutational Signatures and Clonal Hematopoiesis in Intestinal Metaplasia across Countries with Varying Stomach Cancer Incidence.Cancer discovery · 2026Article
- Sex differences in transcription-associated mutagenesis in the human germline.bioRxiv : the preprint server for biology · 2025Article
- Mitigating Cell Cycle Effects in Multi-Omics Data: Solutions and Analytical Frameworks.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Unveiling Replication Timing-Dependent Mutational Biases: Mechanistic Insights from Gene Knockouts and Genotoxins Exposures.International journal of molecular sciences · 2025Article
- Review
- Developmental Changes in Genome Replication Progression in Pluripotent versus Differentiated Human Cells.Genes · 2024Article
- Review
- Cell cycle gene alterations associate with a redistribution of mutation risk across chromosomal domains in human cancers.Nature cancer · 2024Article
- Incomplete reprogramming of DNA replication timing in induced pluripotent stem cells.Cell reports · 2024Article
- Where and when to start: Regulating DNA replication origin activity in eukaryotic genomes.Nucleus (Austin, Tex.) · 2023Review
- Glycidamide-induced hypermutation in yeast single-stranded DNA reveals a ubiquitous clock-like mutational motif in humans.Nucleic acids research · 2023Article
- The landscape of somatic mutations in lymphoblastoid cell lines.Cell genomics · 2023Article
- The evolution of the human DNA replication timing program.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The dynamical organization of the core pluripotency transcription factors responds to differentiation cues in early S-phase.Frontiers in cell and developmental biology · 2023Article
- Regional mutational signature activities in cancer genomes.PLoS computational biology · 2022Article
- Article
- Epigenetic control of chromosome-associated lncRNA genes essential for replication and stability.Nature communications · 2022Article
- Comprehensive analysis of DNA replication timing across 184 cell lines suggests a role for MCM10 in replication timing regulation.Human molecular genetics · 2022Article
- Article
Corrections and comments
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Authors and funding
18 authors at 6 institutions in 2 countries.
Funding
Abstract
DNA replication follows a strict spatiotemporal program that intersects with chromatin structure but has a poorly understood genetic basis. To systematically identify genetic regulators of replication timing, we exploited inter-individual variation in human pluripotent stem cells from 349 individuals. We show that the human genome's replication program is broadly encoded in DNA and identify 1,617 cis-acting replication timing quantitative trait loci (rtQTLs) - sequence determinants of replication initiation. rtQTLs function individually, or in combinations of proximal and distal regulators, and are enriched at sites of histone H3 trimethylation of lysines 4, 9, and 36 together with histone hyperacetylation. H3 trimethylation marks are individually repressive yet synergistically associate with early replication. We identify pluripotency-related transcription factors and boundary elements as positive and negative regulators of replication timing, respectively. Taken together, human replication timing is controlled by a multi-layered mechanism with dozens of effectors working combinatorially and following principles analogous to transcription regulation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.