ArticleNature communications2023
Transcription factor binding site orientation and order are major drivers of gene regulatory activity.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
What it found
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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
57 citing papers in PubMed, 73 citations in OpenAlex.
- Robust regulatory interplay of enhancers, facilitators, and promoters in a native chromatin context.Cell · 2026Article
- A transcription factor by any other name - function beyond DNA binding and transactivation.EMBO reports · 2026Review
- Uniform processing and analysis of IGVF massively parallel reporter assay data with MPRAsnakeflow.Genome research · 2026Article
- Synthetic transcriptional repression systems in plants.Plant cell reports · 2026Review
- Gene regulatory innovations from transposable elements in primate cerebellum development.Nature communications · 2026Article
- Association of APOC2 upstream variant rs10425530 with BMI predicted to overlap with NR2C2, GCM2 and NR2C1 binding sites.Human genomics · 2026Article
- Lentiviral single-cell MPRA of synthetic enhancers reveals motif affinity-based encoding of cell state specificity.Genome biology · 2026Article
- Expression-linked promoter selection (ELiPS) engineers short, strong ubiquitous promoters for gene therapy applications.bioRxiv : the preprint server for biology · 2026Article
- Protocol to predict gene expression from transcriptomic data using PREDICT.STAR protocols · 2026Article
- Decoding cis-regulatory elements in the germline of the human malaria vector Anopheles gambiae.Communications biology · 2026Article
- Article
- Multi-scale dissection, compaction and derivatization of mammalian developmental enhancers.bioRxiv : the preprint server for biology · 2026Article
- PoolParty: streamlined design of DNA sequence libraries in Python.bioRxiv : the preprint server for biology · 2026Article
- Transcription factors Lef1 and Rest stimulate recovery from depressive states.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Article
- Simultaneous epigenomic profiling and regulatory activity measurement using e2MPRA.Nature communications · 2026Article
- HDI-STARR-seq Identifies Functional GH-regulated Sex-Biased Hepatocyte Enhancers Linked to Liver Metabolism and Disease.bioRxiv : the preprint server for biology · 2026Article
- Quantitative modulation of a spatial enhancer through the biophysical properties of a transcription factor binding site.Science advances · 2026Article
- Identification of novel DNA sequence motifs that modulate transcription in T cells.BMC genomics · 2026Article
- JoGo 1.0: the ACTG hierarchical nomenclature and database covering 4.7 million haplotypes across 19,194 human genes.Nucleic acids research · 2026Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
The gene regulatory code and grammar remain largely unknown, precluding our ability to link phenotype to genotype in regulatory sequences. Here, using a massively parallel reporter assay (MPRA) of 209,440 sequences, we examine all possible pair and triplet combinations, permutations and orientations of eighteen liver-associated transcription factor binding sites (TFBS). We find that TFBS orientation and order have a major effect on gene regulatory activity. Corroborating these results with genomic analyses, we find clear human promoter TFBS orientation biases and similar TFBS orientation and order transcriptional effects in an MPRA that tested 164,307 liver candidate regulatory elements. Additionally, by adding TFBS orientation to a model that predicts expression from sequence we improve performance by 7.7%. Collectively, our results show that TFBS orientation and order have a significant effect on gene regulatory activity and need to be considered when analyzing the functional effect of variants on the activity of these sequences.
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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.