ArticleProceedings of the National Academy of Sciences of the United States of America2014
NOTCH1-RBPJ complexes drive target gene expression through dynamic interactions with superenhancers.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 164 papers.
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Who cites it
164 citing papers in PubMed, 266 citations in OpenAlex.
- Systematic investigation reveals extensive Epstein-Barr virus transcriptional regulation of the human genome.Cell genomics · 2026Article
- Direct observation of Notch signaling-induced transcription hubs mediating gene-expression responses.Science advances · 2026Article
- Identifying dendritic cell heterogeneity and potential risk genes in atopic dermatitis: integrative scRNA-seq, bulk RNA-seq analyses and experimental validation.Frontiers in medicine · 2026Article
- Telomere Position Effect-Over Long Distances Acts as a Genome-Wide Epigenetic Regulator Through a Common Alu Element.Aging cell · 2025Article
- Early Notch signals from fibroblastic reticular cells program effector CD8+ T cell differentiation.The Journal of experimental medicine · 2025Article
- The ESCRT protein CHMP5 promotes T cell leukemia by enabling BRD4-p300-dependent transcription.Nature communications · 2025Article
- Regulation of histone H3K27 methylation in inflammation and cancer.Molecular biomedicine · 2025Review
- Genomic clustering tendency of transcription factors reflects phase-separated transcriptional condensates at super-enhancers.Nucleic acids research · 2025Article
- Current progress and future perspective of super-enhancers: a viable and effective bridge between the transcriptional apparatus and disease.Frontiers in genetics · 2025Review
- A multiomic atlas identifies a treatment-resistant, bone marrow progenitor-like cell population in T cell acute lymphoblastic leukemia.Nature cancer · 2025Article
- Identification and Validation of Hub Genes in Hidradenitis Suppurativa.Clinical, cosmetic and investigational dermatology · 2025Article
- The unique functions of Runx1 in skeletal muscle maintenance and regeneration are facilitated by an ETS interaction domain.Development (Cambridge, England) · 2024Article
- Notch induces transcription by stimulating release of paused RNA polymerase II.Genes & development · 2024Article
- Advances in the role of membrane-bound transcription factors in carcinogenesis and therapy.Discover oncology · 2024Review
- Notch1 Phase Separation Coupled Percolation facilitates target gene expression and enhancer looping.Scientific reports · 2024Article
- The cellular Notch1 protein promotes KSHV reactivation in an Rta-dependent manner.Journal of virology · 2024Article
- Notch1 Phase Separation Coupled Percolation facilitates target gene expression and enhancer looping.bioRxiv : the preprint server for biology · 2024Article
- Notch induces transcription by stimulating release of paused RNA Polymerase II.bioRxiv : the preprint server for biology · 2024Article
- Comprehensive genomic features indicative for Notch responsiveness.Nucleic acids research · 2024Article
- AKAP8 promotes ovarian cancer progression and antagonizes PARP inhibitor sensitivity through regulating hnRNPUL1 transcription.iScience · 2024Article
104 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
The main oncogenic driver in T-lymphoblastic leukemia is NOTCH1, which activates genes by forming chromatin-associated Notch transcription complexes. Gamma-secretase-inhibitor treatment prevents NOTCH1 nuclear localization, but most genes with NOTCH1-binding sites are insensitive to gamma-secretase inhibitors. Here, we demonstrate that fewer than 10% of NOTCH1-binding sites show dynamic changes in NOTCH1 occupancy when T-lymphoblastic leukemia cells are toggled between the Notch-on and -off states with gamma-secretase inhibiters. Dynamic NOTCH1 sites are functional, being highly associated with Notch target genes, are located mainly in distal enhancers, and frequently overlap with RUNX1 binding. In line with the latter association, we show that expression of IL7R, a gene with key roles in normal T-cell development and in T-lymphoblastic leukemia, is coordinately regulated by Runx factors and dynamic NOTCH1 binding to distal enhancers. Like IL7R, most Notch target genes and associated dynamic NOTCH1-binding sites cooccupy chromatin domains defined by constitutive binding of CCCTC binding factor, which appears to restrict the regulatory potential of dynamic NOTCH1 sites. More remarkably, the majority of dynamic NOTCH1 sites lie in superenhancers, distal elements with exceptionally broad and high levels of H3K27ac. Changes in Notch occupancy produces dynamic alterations in H3K27ac levels across the entire breadth of superenhancers and in the promoters of Notch target genes. These findings link regulation of superenhancer function to NOTCH1, a master regulatory factor and potent oncoprotein in the context of immature T cells, and delineate a generally applicable roadmap for identifying functional Notch sites in cellular genomes.
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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.