ArticleNature genetics2016
Hierarchy within the mammary STAT5-driven Wap super-enhancer.
Article in Nature genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 179 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
179 citing papers in PubMed, 309 citations in OpenAlex.
- Robust regulatory interplay of enhancers, facilitators, and promoters in a native chromatin context.Cell · 2026Article
- Article
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- Asymmetry and redundancy of STAT5 paralogs across CD8Communications biology · 2026Article
- Facilitators may represent a new class of regulatory elements.Current opinion in genetics & development · 2026Review
- Extensive enhancer crosstalk controls PPARG2 activation during adipogenesis.Nature communications · 2026Article
- Review
- Review
- Noncoding function of super enhancer derivedRNA biology · 2025Review
- Unveiling the regulatory potential of the non-coding genome: Insights from the human genome project to precision medicine.Genes & diseases · 2025Review
- Aberrant Enhancer Regulation, Phase Separation, and Autoimmune Diseases.Clinical reviews in allergy & immunology · 2025Review
- STAT5B leukemic mutations, altering SH2 tyrosine 665, have opposing impacts on immune gene programs.Life science alliance · 2025Article
- Assessment of the histone mark-based epigenomic landscape in human myometrium at term pregnancy.eLife · 2025Article
- Disease-Associated Mutations of the STAT5B SH2 Domain Regulate Cytokine-Driven Enhancer Function and Mammary Development.Journal of mammary gland biology and neoplasia · 2025Article
- Bidirectional epigenetic editing reveals hierarchies in gene regulation.Nature biotechnology · 2025Article
- Super-enhancers in tumors: unraveling recent advances in their role in Oncogenesis and the emergence of targeted therapies.Journal of translational medicine · 2025Review
- Modular organization of enhancer network provides transcriptional robustness in mammalian development.Nucleic acids research · 2025Article
- Super-silencer perturbation by EZH2 and REST inhibition leads to large loss of chromatin interactions and reduction in cancer growth.Nature structural & molecular biology · 2025Article
- Super-enhancers in immune system regulation: mechanisms, pathological reprogramming, and therapeutic opportunities.Frontiers in immunology · 2025Review
- A mathematical model clarifies the ABC Score formula used in enhancer-gene prediction.bioRxiv : the preprint server for biology · 2024Article
119 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Super-enhancers comprise dense transcription factor platforms highly enriched for active chromatin marks. A paucity of functional data led us to investigate the role of super-enhancers in the mammary gland, an organ characterized by exceptional gene regulatory dynamics during pregnancy. ChIP-seq analysis for the master regulator STAT5A, the glucocorticoid receptor, H3K27ac and MED1 identified 440 mammary-specific super-enhancers, half of which were associated with genes activated during pregnancy. We interrogated the Wap super-enhancer, generating mice carrying mutations in STAT5-binding sites within its constituent enhancers. Individually, the most distal site displayed the greatest enhancer activity. However, combinatorial mutation analysis showed that the 1,000-fold induction in gene expression during pregnancy relied on all enhancers. Disabling the binding sites of STAT5, NFIB and ELF5 in the proximal enhancer incapacitated the entire super-enhancer. Altogether, these data suggest a temporal and functional enhancer hierarchy. The identification of mammary-specific super-enhancers and the mechanistic exploration of the Wap locus provide insights into the regulation of cell-type-specific expression of hormone-sensing genes.
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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.