ArticleGenome biology2019
The first enhancer in an enhancer chain safeguards subsequent enhancer-promoter contacts from a distance.
Article in Genome biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Decoding 3D chromatin architecture reveals distinct enhancer classes underlying hierarchical gene regulation in prostate cancer.Genome biology · 2026Article
- Enhancer-dependent gene regulation in space, time, and malignancies.International journal of cancer · 2026Review
- Supervised learning of enhancer-promoter specificity based on genome-wide perturbation studies highlights areas for improvement in learning.Bioinformatics (Oxford, England) · 2024Article
- Building Haplotype-Resolved 3D Genome Maps of Chicken Skeletal Muscle.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Haplotype-resolved 3D chromatin architecture of the hybrid pig.Genome research · 2024Article
- STAT3-Mediated Promoter-Enhancer Interaction Up-Regulates Inhibitor of DNA Binding 1 (International journal of molecular sciences · 2023Article
- Bioinformatic Evaluation of Features on Cis-regulatory Elements at 6q25.1.Bioinformatics and biology insights · 2023Review
- Article
- Dynamic 3D genome reorganization during development and metabolic stress of the porcine liver.Cell discovery · 2022Article
- CT-FOCS: a novel method for inferring cell type-specific enhancer-promoter maps.Nucleic acids research · 2022Article
- Duplications disrupt chromatin architecture and rewire GPR101-enhancer communication in X-linked acrogigantism.American journal of human genetics · 2022Article
- Application of the 3C Method to Study the Developmental Genes inFrontiers in genetics · 2022Article
- Transcriptional enhancers and their communication with gene promoters.Cellular and molecular life sciences : CMLS · 2021Review
- Mechanisms of enhancer action: the known and the unknown.Genome biology · 2021Review
- Cohesin-Dependent and -Independent Mechanisms Mediate Chromosomal Contacts between Promoters and Enhancers.Cell reports · 2020Article
- Evolution of Regulated Transcription.Cells · 2020Review
- Transcriptional activation during cell reprogramming correlates with the formation of 3D open chromatin hubs.Nature communications · 2020Article
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRobustness and evolutionary stability of gene expression in the human genome are established by an array of redundant enhancers.
resultsUsing Hi-C data in multiple cell lines, we report a comprehensive map of promoters and active enhancers connected by chromatin contacts, spanning 9000 enhancer chains in 4 human cell lines associated with 2600 human genes. We find that the first enhancer in a chain that directly contacts the target promoter is commonly located at a greater genomic distance from the promoter than the second enhancer in a chain, 96 kb vs. 45 kb, respectively. The first enhancer also features higher similarity to the promoter in terms of tissue specificity and higher enrichment of loop factors, suggestive of a stable primary contact with the promoter. In contrast, a chain of enhancers which connects to the target promoter through a neutral DNA segment instead of an enhancer is associated with a significant decrease in target gene expression, suggesting an important role of the first enhancer in initiating transcription using the target promoter and bridging the promoter with other regulatory elements in the locus.
conclusionsThe widespread chained structure of gene enhancers in humans reveals that the primary, critical enhancer is distal, commonly located further away than other enhancers. This first, distal enhancer establishes contacts with multiple regulatory elements and safeguards a complex regulatory program of its target gene.
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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.