ArticleNature biotechnology2016
Genome-scale high-resolution mapping of activating and repressive nucleotides in regulatory regions.
Article in Nature biotechnology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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Who cites it
105 citing papers in PubMed, 180 citations in OpenAlex.
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- Extensive binding of poorly characterized human transcription factors to genomic dark matter.Nature communications · 2026Article
- Multi-scale dissection, compaction and derivatization of mammalian developmental enhancers.bioRxiv : the preprint server for biology · 2026Article
- Retracing and rewriting the evolutionary trajectories of mammalian developmental enhancers.bioRxiv : the preprint server for biology · 2026Article
- B-type lamins maintain transcriptional homeostasis by spatially controlling chromatin-speckle proximity.Nucleic acids research · 2026Article
- Liver single-nucleus multiome profiling reveals cell-type mechanisms for cardiometabolic traits.American journal of human genetics · 2026Article
- Comprehensive evaluation of diverse massively parallel reporter assays to functionally characterize human enhancers genome-wide.Genome biology · 2025Article
- Applications of high-throughput reporter assays to gene regulation studies.Current opinion in structural biology · 2025Review
- Super-silencers are crucial for development and carcinogenesis in B cells.Nature communications · 2025Article
- Combinatorial DNMTs and EZH2 inhibition reprograms the H3K27me3 and DNAme-mediated onco-epigenome to suppress multiple myeloma proliferation.Scientific reports · 2025Article
- Context-dependent regulatory variants in Alzheimer's disease.bioRxiv : the preprint server for biology · 2025Article
- Iterative deep learning design of human enhancers exploits condensed sequence grammar to achieve cell-type specificity.Cell systems · 2025Article
- Genomic and cellular context-dependent expression of the human ELMO1 gene transcript variants.Gene · 2025Article
- ChromActivity: integrative epigenomic and functional characterization assay based annotation of regulatory activity across diverse human cell types.Genome biology · 2025Article
- Article
- Modeling and designing enhancers by introducing and harnessing transcription factor binding units.Nature communications · 2025Article
- Abundant repressor binding sites in human enhancers are associated with the fine-tuning of gene regulation.iScience · 2025Article
- AnFrontiers in genetics · 2025Article
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- Deciphering the functional impact of Alzheimer's Disease-associated variants in resting and proinflammatory immune cells.medRxiv : the preprint server for health sciences · 2024Article
45 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Massively parallel reporter assays (MPRAs) enable nucleotide-resolution dissection of transcriptional regulatory regions, such as enhancers, but only few regions at a time. Here we present a combined experimental and computational approach, Systematic high-resolution activation and repression profiling with reporter tiling using MPRA (Sharpr-MPRA), that allows high-resolution analysis of thousands of regions simultaneously. Sharpr-MPRA combines dense tiling of overlapping MPRA constructs with a probabilistic graphical model to recognize functional regulatory nucleotides, and to distinguish activating and repressive nucleotides, using their inferred contribution to reporter gene expression. We used Sharpr-MPRA to test 4.6 million nucleotides spanning 15,000 putative regulatory regions tiled at 5-nucleotide resolution in two human cell types. Our results recovered known cell-type-specific regulatory motifs and evolutionarily conserved nucleotides, and distinguished known activating and repressive motifs. Our results also showed that endogenous chromatin state and DNA accessibility are both predictive of regulatory function in reporter assays, identified retroviral elements with activating roles, and uncovered 'attenuator' motifs with repressive roles in active chromatin.
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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.