ArticleGenome research2014
High-throughput functional testing of ENCODE segmentation predictions.
Article in Genome research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 156 papers, 1 of them a synthesis that pooled it.
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Who cites it
156 citing papers in PubMed, 1 synthesis or guideline pooled it.
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- Exploring the roles of conserved context-dependent cis-regulatory elements (cdCREs) in multicellularity, human health and disease.The FEBS journal · 2025Review
- Comprehensive evaluation of diverse massively parallel reporter assays to functionally characterize human enhancers genome-wide.Genome biology · 2025Article
- Massively parallel reporter assay reveals promoter-, position-, and strand-specific effects in transcription start sites.bioRxiv : the preprint server for biology · 2025Article
- Identification of functional non-coding variants associated with orofacial cleft.Nature communications · 2025Article
- Prediction of target genes and functional types of cis-regulatory modules in the human genome reveals their distinct properties.BMC biology · 2025Article
- H3K79 methylation and H3K36 trimethylation synergistically regulate gene expression in pluripotent stem cells.Science advances · 2025Article
- A suite of enhancer AAVs and transgenic mouse lines for genetic access to cortical cell types.Cell · 2025Article
- Large-scale discovery of potent, compact and erythroid specific enhancers for gene therapy vectors.Nature communications · 2025Article
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- Active learning of enhancers and silencers in the developing neural retina.Cell systems · 2025Article
- Massively parallel characterization of insulator activity across the genome.Nature communications · 2024Article
- A suite of enhancer AAVs and transgenic mouse lines for genetic access to cortical cell types.bioRxiv : the preprint server for biology · 2024Article
- Oncogenic Enhancers in Leukemia.Blood cancer discovery · 2024Review
- Identification of Regulatory Elements in Primary Sensory Neurons Involved in Trauma-Induced Neuropathic Pain.Molecular neurobiology · 2024Article
- Optimizing sequence design strategies for perturbation MPRAs: a computational evaluation framework.Nucleic acids research · 2024Article
- Proformer: a hybrid macaron transformer model predicts expression values from promoter sequences.BMC bioinformatics · 2024Article
96 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors.
Funding
Abstract
The histone modification state of genomic regions is hypothesized to reflect the regulatory activity of the underlying genomic DNA. Based on this hypothesis, the ENCODE Project Consortium measured the status of multiple histone modifications across the genome in several cell types and used these data to segment the genome into regions with different predicted regulatory activities. We measured the cis-regulatory activity of more than 2000 of these predictions in the K562 leukemia cell line. We tested genomic segments predicted to be Enhancers, Weak Enhancers, or Repressed elements in K562 cells, along with other sequences predicted to be Enhancers specific to the H1 human embryonic stem cell line (H1-hESC). Both Enhancer and Weak Enhancer sequences in K562 cells were more active than negative controls, although surprisingly, Weak Enhancer segmentations drove expression higher than did Enhancer segmentations. Lower levels of the covalent histone modifications H3K36me3 and H3K27ac, thought to mark active enhancers and transcribed gene bodies, associate with higher expression and partly explain the higher activity of Weak Enhancers over Enhancer predictions. While DNase I hypersensitivity (HS) is a good predictor of active sequences in our assay, transcription factor (TF) binding models need to be included in order to accurately identify highly expressed sequences. Overall, our results show that a significant fraction (-26%) of the ENCODE enhancer predictions have regulatory activity, suggesting that histone modification states can reflect the cis-regulatory activity of sequences in the genome, but that specific sequence preferences, such as TF-binding sites, are the causal determinants of cis-regulatory activity.
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