ArticleGenes & development2017
Dynamic assembly and activation of estrogen receptor α enhancers through coregulator switching.
Article in Genes & development, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 68 citations in OpenAlex.
- Advances in Mechanism of Action and Efficacy of CBP/p300 Inhibitors in Different Subtypes of Breast Cancer.Molecules (Basel, Switzerland) · 2026Review
- MED1 IDR deacetylation controls stress responsive genes through RNA Pol II recruitment.Nature chemical biology · 2026Article
- Altered cofactor recruitment and nucleosome dynamics underlie bisphenol A's impact on ERα-mediated transcriptional bursting.iScience · 2025Article
- Comprehensive functional annotation of ESR1-driven enhancers in breast cancer reveals hierarchical activity independent of genomic and epigenomic contexts.Genome research · 2025Article
- Intracellular Retention of Estradiol Is Mediated by GRAM Domain-Containing Protein ASTER-B in Breast Cancer Cells.Molecular cancer research : MCR · 2025Article
- Decoding estrogen receptor and GPER biology: structural insights and therapeutic advances in ERα-positive breast cancer.Frontiers in oncology · 2025Review
- Intracellular Retention of Estradiol is Mediated by GRAM Domain-Containing Protein ASTER-B in Breast Cancer Cells.bioRxiv : the preprint server for biology · 2024Article
- Mediator MED23 controls oligodendrogenesis and myelination by modulating Sp1/P300-directed gene programs.Cell discovery · 2024Article
- Relaxin Modulates the Genomic Actions and Biological Effects of Estrogen in the Myometrium.Endocrinology · 2024Article
- Relaxin Modulates the Genomic Actions and Biological Effects of Estrogen in the Myometrium.bioRxiv : the preprint server for biology · 2024Article
- ZMIZ1 enhances ERα-dependent expression of E2F2 in breast cancer.Journal of molecular endocrinology · 2024Article
- Genome-wide identification of transcriptional enhancers during human placental development and association with function, differentiation, and disease†.Biology of reproduction · 2023Article
- Regulation of the RNA polymerase II pre-initiation complex by its associated coactivators.Nature reviews. Genetics · 2023Review
- PAXIP1 and STAG2 converge to maintain 3D genome architecture and facilitate promoter/enhancer contacts to enable stress hormone-dependent transcription.Nucleic acids research · 2023Article
- Estrogen Receptor Signaling in Breast Cancer.Cancers · 2023Review
- Serine starvation silences estrogen receptor signaling through histone hypoacetylation.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Post-translational modifications of histones: Mechanisms, biological functions, and therapeutic targets.MedComm · 2023Review
- ERK1/2-RSK regulation of oestrogen homeostasis.The FEBS journal · 2023Review
- The Mediator complex as a master regulator of transcription by RNA polymerase II.Nature reviews. Molecular cell biology · 2022Review
- Transcriptional enhancers at 40: evolution of a viral DNA element to nuclear architectural structures.Trends in genetics : TIG · 2022Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Although many features of active transcriptional enhancers have been defined by genomic assays, we lack a clear understanding of the order of events leading to enhancer formation and activation as well as the dynamics of coregulator interactions within the enhancer complex. Here, we used selective loss- or gain-of-function mutants of estrogen receptor α (ERα) to define two distinct phases of ligand-dependent enhancer formation. In the first phase (0-20 min), p300 is recruited to ERα by Mediator as well as p300's acetylhistone-binding bromodomain to promote initial enhancer formation, which is not competent for sustained activation. In the second phase (20-45 min), p300 is recruited to ERα by steroid receptor coregulators (SRCs) for enhancer maturation and maintenance. Successful transition between these two phases ("coregulator switching") is required for proper enhancer function. Failure to recruit p300 during either phase leads to abortive enhancer formation and a lack of target gene expression. Our results reveal an ordered and cooperative assembly of ERα enhancers requiring functional interplay among p300, Mediator, and SRCs, which has implications for hormone-dependent gene regulation in breast cancers. More broadly, our results demonstrate the unexpectedly dynamic nature of coregulator interactions within enhancer complexes, which are likely to be a defining feature of all enhancers.
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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.