ArticleMolecular cell2024
Genomic context sensitizes regulatory elements to genetic disruption.
Article in Molecular cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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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.
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Who cites it
7 citing papers in PubMed.
- Synthetic Regulatory Genomics.Annual review of genomics and human genetics · 2026Review
- Improved vector toolkit for genome writing in mammalian cells.bioRxiv : the preprint server for biology · 2026Article
- Review
- Configuring the Code: Enhancer-Promoter Arrangement and Transcriptional Regulation.Journal of molecular biology · 2026Review
- Iterative improvement of deep learning models using synthetic regulatory genomics.Genome research · 2025Article
- Human Genome REWRITE for Off-the-Shelf Stem Cells Reveals an "Epigenetic Ghost".bioRxiv : the preprint server for biology · 2025Article
- Engineering structural variants to interrogate genome function.Nature genetics · 2024Review
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11 authors.
Funding
Abstract
Genomic context critically modulates regulatory function but is difficult to manipulate systematically. The murine insulin-like growth factor 2 (Igf2)/H19 locus is a paradigmatic model of enhancer selectivity, whereby CTCF occupancy at an imprinting control region directs downstream enhancers to activate either H19 or Igf2. We used synthetic regulatory genomics to repeatedly replace the native locus with 157-kb payloads, and we systematically dissected its architecture. Enhancer deletion and ectopic delivery revealed previously uncharacterized long-range regulatory dependencies at the native locus. Exchanging the H19 enhancer cluster with the Sox2 locus control region (LCR) showed that the H19 enhancers relied on their native surroundings while the Sox2 LCR functioned autonomously. Analysis of regulatory DNA actuation across cell types revealed that these enhancer clusters typify broader classes of context sensitivity genome wide. These results show that unexpected dependencies influence even well-studied loci, and our approach permits large-scale manipulation of complete loci to investigate the relationship between regulatory architecture and function.
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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.