ArticleeLife2021
Evidence for additive and synergistic action of mammalian enhancers during cell fate determination.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 124 citations in OpenAlex.
- Pig Matrix: a matched multiomics 3D regulatory genomics database for evolutionary and comparative analyses in pigs.Molecular biology and evolution · 2026Article
- Regulation of lineage reprogramming by dynamic chromatin SUMOylation.Cellular and molecular life sciences : CMLS · 2026Article
- The differentiation of myeloid progenitors is effected by cascading waves of coordinated gene expression that remodel cellular physiology in a characteristic sequence.PLoS computational biology · 2026Article
- Accessibility at a primed distal Fshb-Kcna4 super-enhancer is facilitated by Foxl2 during gonadotrope differentiation.Endocrinology · 2026Article
- Boolean logic links chromatin accessibility states to gene expression variability across cell types.Nucleic acids research · 2026Article
- Extensive enhancer crosstalk controls PPARG2 activation during adipogenesis.Nature communications · 2026Article
- Remodeling ofScience advances · 2026Article
- Enhancer Trajectories in Lineage Commitment: Regulatory Logic of States and Cooperation.Biomolecules · 2026Review
- Characterization of a cis-regulatory element upstream of matrix metalloproteinase-9.Scientific reports · 2025Article
- The chronODE framework for modelling multi-omic time series with ordinary differential equations and machine learning.Nature communications · 2025Article
- Igf2 adult-specific skeletal muscle enhancer activity revealed in mice with intergenic CTCF boundary deletion.PLoS genetics · 2025Article
- Modulating immune cell fate and inflammation through CRISPR-mediated DNA methylation editing.Science advances · 2025Article
- CTCF depletion decouples enhancer-mediated gene activation from chromatin hub formation.Nature structural & molecular biology · 2025Article
- Adversarial attack of sequence-free enhancer prediction identifies chromatin architecture.Bioinformatics (Oxford, England) · 2025Article
- Discovery of NANOG enhancers and their essential roles in self-renewal and differentiation in human embryonic stem cells.Stem cell reports · 2025Article
- Promoter-proximal RNA polymerase II termination regulates transcription during human cell type transition.Nature structural & molecular biology · 2025Article
- Auricular malformations are driven by copy number variations in a hierarchical enhancer cluster and a dominant enhancer recapitulates human pathogenesis.Nature communications · 2025Article
- The application of irreversible genomic states to define and trace ancient cell type homologies.EvoDevo · 2025Article
- Three-dimensional regulatory hubs support oncogenic programs in glioblastoma.Molecular cell · 2025Article
- Epigenetic disruption of adipogenic gene enhancers in dedifferentiated liposarcomas and its therapeutic value.Frontiers in oncology · 2025Article
14 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Enhancer activity drives cell differentiation and cell fate determination, but it remains unclear how enhancers cooperate during these processes. Here we investigate enhancer cooperation during transdifferentiation of human leukemia B-cells to macrophages. Putative enhancers are established by binding of the pioneer factor C/EBPα followed by chromatin opening and enhancer RNA (eRNA) synthesis from H3K4-monomethylated regions. Using eRNA synthesis as a proxy for enhancer activity, we find that most putative enhancers cooperate in an additive way to regulate transcription of assigned target genes. However, transcription from 136 target genes depends exponentially on the summed activity of its putative paired enhancers, indicating that these enhancers cooperate synergistically. The target genes are cell type-specific, suggesting that enhancer synergy can contribute to cell fate determination. Enhancer synergy appears to depend on cell type-specific transcription factors, and such interacting enhancers are not predicted from occupancy or accessibility data that are used to detect superenhancers.
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Registered trials
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.