ArticleGenome research2020
Dissecting the regulatory activity and sequence content of loci with exceptional numbers of transcription factor associations.
Article in Genome research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
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- Microglial epigenetic memory is associated with accelerated resolution of inflammatory pain induced by prophylactic macrophage-derived small extracellular vesicles.bioRxiv : the preprint server for biology · 2026Article
- Microglial Epigenetic Memory is Associated with Accelerated Resolution of Inflammatory Pain Induced by Prophylactic Macrophage-Derived Small Extracellular Vesicles.Journal of inflammation research · 2026Article
- Control of Gene Expression by Proteins That Bind Many Alternative Nucleic Acid Structures Through the Same Domain.International journal of molecular sciences · 2025Article
- Chromatin-associated condensates as an inspiration for the system architecture of future DNA computers.Annals of the New York Academy of Sciences · 2025Review
- Early tolerance and late persistence as alternative drug responses in cancer.Nature communications · 2025Article
- Systematic functional characterization of non-coding regulatory SNPs associated with central obesity.American journal of human genetics · 2025Article
- Functional characteristics and computational model of abundant hyperactive loci in the human genome.eLife · 2024Article
- A Compendium of G-Flipon Biological Functions That Have Experimental Validation.International journal of molecular sciences · 2024Review
- Functional characteristics and computational model of abundant hyperactive loci in the human genome.bioRxiv : the preprint server for biology · 2024Article
- Characterization of human transcription factor function and patterns of gene regulation in HepG2 cells.Genome research · 2023Article
- Clustered and diverse transcription factor binding underlies cell type specificity of enhancers for housekeeping genes.Genome research · 2023Article
- Integrating massive RNA-seq data to elucidate transcriptome dynamics in Drosophila melanogaster.Briefings in bioinformatics · 2023Article
- Characterizing the targets of transcription regulators by aggregating ChIP-seq and perturbation expression data sets.Genome research · 2023Article
- Innate Immune Memory and the Host Response to Infection.Journal of immunology (Baltimore, Md. : 1950) · 2022Review
- Master lineage transcription factors anchor trans mega transcriptional complexes at highly accessible enhancer sites to promote long-range chromatin clustering and transcription of distal target genes.Nucleic acids research · 2021Article
- Genome-wide strand asymmetry in massively parallel reporter activity favors genic strands.Genome research · 2021Article
- G-quadruplexes are transcription factor binding hubs in human chromatin.Genome biology · 2021Article
- A flexible repertoire of transcription factor binding sites and a diversity threshold determines enhancer activity in embryonic stem cells.Genome research · 2021Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
DNA-associated proteins (DAPs) classically regulate gene expression by binding to regulatory loci such as enhancers or promoters. As expanding catalogs of genome-wide DAP binding maps reveal thousands of loci that, unlike the majority of conventional enhancers and promoters, associate with dozens of different DAPs with apparently little regard for motif preference, an understanding of DAP association and coordination at such regulatory loci is essential to deciphering how these regions contribute to normal development and disease. In this study, we aggregated publicly available ChIP-seq data from 469 human DAPs assayed in three cell lines and integrated these data with an orthogonal data set of 352 nonredundant, in vitro-derived motifs mapped to the genome within DNase I hypersensitivity footprints to characterize regions with high numbers of DAP associations. We establish a generalizable definition for high occupancy target (HOT) loci and identify putative driver DAP motifs in HepG2 cells, including HNF4A, SP1, SP5, and ETV4, that are highly prevalent and show sequence conservation at HOT loci. The number of different DAPs associated with an element is positively associated with evidence of regulatory activity, and by systematically mutating 245 HOT loci with a massively parallel mutagenesis assay, we localized regulatory activity to a central core region that depends on the motif sequences of our previously nominated driver DAPs. In sum, this work leverages the increasingly large number of DAP motif and ChIP-seq data publicly available to explore how DAP associations contribute to genome-wide transcriptional regulation.
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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 Socratic graph.