ArticleNucleic acids research2018
Genomic dissection of enhancers uncovers principles of combinatorial regulation and cell type-specific wiring of enhancer-promoter contacts.
Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
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- A non-coding GWAS variant impacts anthracycline-induced cardiotoxic phenotypes in human iPSC-derived cardiomyocytes.Nature communications · 2022Article
- Crosstalk between p38 MAPK and GR Signaling.International journal of molecular sciences · 2022Review
- Multimodal regulatory elements within a hormone-specific super enhancer control a heterogeneous transcriptional response.Molecular cell · 2022Article
- Assessing genome-wide dynamic changes in enhancer activity during early mESC differentiation by FAIRE-STARR-seq.Nucleic acids research · 2021Article
- Characterization of the regulatory 5'-flanking region of bovine mucin 2 (MUC2) gene.Molecular and cellular biochemistry · 2021Article
- Glucocorticoid receptor wields chromatin interactions to tune transcription for cytoskeleton stabilization in podocytes.Communications biology · 2021Article
- Genome-wide binding potential and regulatory activity of the glucocorticoid receptor's monomeric and dimeric forms.Nature communications · 2021Article
- Mechanisms and Clinical Applications of Glucocorticoid Steroids in Muscular Dystrophy.Journal of neuromuscular diseases · 2021Review
- Promoter-interacting expression quantitative trait loci are enriched for functional genetic variants.Nature genetics · 2021Article
- A preliminary computational outputs versus experimental results: Application of sTRAP, a biophysical tool for the analysis of SNPs of transcription factor-binding sites.Molecular genetics & genomic medicine · 2020Article
- IL-1 Transcriptional Responses to Lipopolysaccharides Are Regulated by a Complex of RNA Binding Proteins.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Sufficiency analysis of estrogen responsive enhancers using synthetic activators.Life science alliance · 2019Article
- Stress-glucocorticoid-TSC22D3 axis compromises therapy-induced antitumor immunity.Nature medicine · 2019Article
- Expanding the repertoire of glucocorticoid receptor target genes by engineering genomic response elements.Life science alliance · 2019Article
- Applications of ENCODE data to Systematic Analyses via Data Integration.Current opinion in systems biology · 2018Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genomic binding of transcription factors, like the glucocorticoid receptor (GR), is linked to the regulation of genes. However, as we show here, GR binding is a poor predictor of GR-dependent gene regulation even when taking the 3D organization of the genome into account. To connect GR binding sites to the regulation of genes in the endogenous genomic context, we turned to genome editing. By deleting GR binding sites, individually or in combination, we uncovered how cooperative interactions between binding sites contribute to the regulation of genes. Specifically, for the GR target gene GILZ, we show that the simultaneous presence of a cluster of GR binding sites is required for the activity of an individual enhancer and that the GR-dependent regulation of GILZ depends on multiple GR-bound enhancers. Further, by deleting GR binding sites that are shared between different cell types, we show how cell type-specific genome organization and enhancer-blocking can result in cell type-specific wiring of promoter-enhancer contacts. This rewiring allows an individual GR binding site shared between different cell types to direct the expression of distinct transcripts and thereby contributes to the cell type-specific consequences of glucocorticoid signaling.
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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.