ArticleMolecular cell2023
Synthetic regulatory genomics uncovers enhancer context dependence at the Sox2 locus.
Article in Molecular cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 65 citations in OpenAlex.
- Robust regulatory interplay of enhancers, facilitators, and promoters in a native chromatin context.Cell · 2026Article
- TheiScience · 2026Article
- Mechanisms and functional implications of long-range enhancer-dependent gene regulation.Nature genetics · 2026Review
- Article
- ExoShorkie: predicting RNA-seq coverage of exogenous genomes in yeast by transfer learning.Bioinformatics (Oxford, England) · 2026Article
- Synthetic Regulatory Genomics.Annual review of genomics and human genetics · 2026Review
- Enhancer control of promoter activity and variability via frequency modulation of clustered transcriptional bursts.Nature genetics · 2026Article
- Promoter strength and position govern promoter competition through transcript-dependent insulation.Nature genetics · 2026Article
- Synthetic rewriting of the IGH locus.Cell genomics · 2026Article
- Cohesin-mediated loop extrusion and enhancer-associated factors additively contribute toGenes & development · 2026Article
- Direct roles of long non-coding RNAs in transcription activation.Nature structural & molecular biology · 2026Review
- Facilitators may represent a new class of regulatory elements.Current opinion in genetics & development · 2026Review
- Improved vector toolkit for genome writing in mammalian cells.bioRxiv : the preprint server for biology · 2026Article
- Extensive enhancer crosstalk controls PPARG2 activation during adipogenesis.Nature communications · 2026Article
- Synergy between regulatory elements can render cohesin dispensable for distal enhancer function.Science (New York, N.Y.) · 2026Article
- Review
- Synthetic rewriting technologies in mammalian cells.Nature communications · 2026Review
- A methodology to reduce the localization error in multi-loci microscopy provides new insights into enhancer biology.PLoS computational biology · 2025Article
- Single-cell multiomics analysis reveals CTCF as a key regulator of lung morphogenesis and progenitor maintenance.Nature communications · 2025Article
- Iterative improvement of deep learning models using synthetic regulatory genomics.Genome research · 2025Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Sox2 expression in mouse embryonic stem cells (mESCs) depends on a distal cluster of DNase I hypersensitive sites (DHSs), but their individual contributions and degree of interdependence remain a mystery. We analyzed the endogenous Sox2 locus using Big-IN to scarlessly integrate large DNA payloads incorporating deletions, rearrangements, and inversions affecting single or multiple DHSs, as well as surgical alterations to transcription factor (TF) recognition sequences. Multiple mESC clones were derived for each payload, sequence-verified, and analyzed for Sox2 expression. We found that two DHSs comprising a handful of key TF recognition sequences were each sufficient for long-range activation of Sox2 expression. By contrast, three nearby DHSs were entirely context dependent, showing no activity alone but dramatically augmenting the activity of the autonomous DHSs. Our results highlight the role of context in modulating genomic regulatory element function, and our synthetic regulatory genomics approach provides a roadmap for the dissection of other genomic loci.
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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.