ArticleNature genetics2022
Sequence determinants of human gene regulatory elements.
Article in Nature genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 131 papers, 1 of them a synthesis that pooled it.
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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
131 citing papers in PubMed, 1 synthesis or guideline pooled it, 211 citations in OpenAlex.
- Genetic variation in cis-regulatory domains suggests cell type-specific regulatory mechanisms in immunity.Communications biology · 2023Pooled it
- Mechanisms and functional implications of long-range enhancer-dependent gene regulation.Nature genetics · 2026Review
- Cross-Model Uncertainty-Aware Minimal Editing of Cis-Regulatory Elements for Cell-Type-Selective Design.Genes · 2026Article
- Toward generalizable and interpretable AI in regulatory genomics.Nature genetics · 2026Review
- Opportunities for artificial intelligence and synthetic biology in designing living drug delivery systems.Advanced drug delivery reviews · 2026Review
- Developmental expression of the skeletal muscle determination gene,bioRxiv : the preprint server for biology · 2026Article
- Lentiviral single-cell MPRA of synthetic enhancers reveals motif affinity-based encoding of cell state specificity.Genome biology · 2026Article
- Using a modular massively parallel reporter assay to discover context-dependent regulatory activity in type 2 diabetes-linked noncoding regions.HGG advances · 2026Article
- Segmentally Duplicated Regulatory Elements Undergo Human-Specific Rewiring.Molecular biology and evolution · 2026Article
- Intrinsic promoter responsiveness dictates sensitivity to transcriptional activation by enhancers.bioRxiv : the preprint server for biology · 2026Article
- Multiplexed Retinoic Acid Signal Reporters for In Vivo and In Vitro Use.Genesis (New York, N.Y. : 2000) · 2026Article
- Pervasive Transcription in the Human Genome Exceeds Background Noise.Genome biology and evolution · 2026Article
- Designing DNA With Tunable Regulatory Activity Using Discrete Diffusion.bioRxiv : the preprint server for biology · 2026Article
- Multi-scale dissection, compaction and derivatization of mammalian developmental enhancers.bioRxiv : the preprint server for biology · 2026Article
- STARR-CRAAVT: A platform to identify cell type-specific regulatory elements for next-generation gene therapy.iScience · 2026Article
- Facilitators may represent a new class of regulatory elements.Current opinion in genetics & development · 2026Review
- Engineering genetic elements for microbial protein expression systems: Advances, challenges, applications, and prospects.Synthetic and systems biotechnology · 2026Review
- Article
- Chromatin accessibility landscapes define stromal cell identities across tissues.Communications biology · 2026Article
- Article
71 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 5 countries.
Funding
Abstract
DNA can determine where and when genes are expressed, but the full set of sequence determinants that control gene expression is unknown. Here, we measured the transcriptional activity of DNA sequences that represent an ~100 times larger sequence space than the human genome using massively parallel reporter assays (MPRAs). Machine learning models revealed that transcription factors (TFs) generally act in an additive manner with weak grammar and that most enhancers increase expression from a promoter by a mechanism that does not appear to involve specific TF-TF interactions. The enhancers themselves can be classified into three types: classical, closed chromatin and chromatin dependent. We also show that few TFs are strongly active in a cell, with most activities being similar between cell types. Individual TFs can have multiple gene regulatory activities, including chromatin opening and enhancing, promoting and determining transcription start site (TSS) activity, consistent with the view that the TF binding motif is the key atomic unit of gene expression.
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What OpenQuestion holds
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.