ArticlePLoS genetics2020
Ligand dependent gene regulation by transient ERα clustered enhancers.
Article in PLoS genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 42 citations in OpenAlex.
- Beyond the canonical view: steroid receptor network plasticity and mechanosensitive chromatin integration in breast cancer.NAR cancer · 2026Review
- Ligand-dependent enhancer activation indirectly modulates non-target promoters in a chromatin domain.eLife · 2026Article
- ChIP happens: from biochemical origins to the modern omics toolbox for understanding steroid hormone receptors.The Biochemical journal · 2026Review
- The role of LLPS of biomacromolecules in the gonads and related diseases.Frontiers in endocrinology · 2026Review
- Paused RNA polymerase primes promoters via RNA-mediated stabilisation of transcription factor ERα.Nature communications · 2025Article
- RACK7 senses and fine-tunes enhancer activity.iScience · 2025Article
- Comprehensive functional annotation of ESR1-driven enhancers in breast cancer reveals hierarchical activity independent of genomic and epigenomic contexts.Genome research · 2025Article
- RVINN: a flexible modeling for inferring dynamic transcriptional and post-transcriptional regulation using physics-informed neural networks.Bioinformatics (Oxford, England) · 2025Article
- Mineralocorticoid receptor phase separation modulates cardiac preservation.Nature cardiovascular research · 2025Article
- Zooming into Gene Activation: Estrogen Receptor α Dimerization and DNA Binding Visualized by High-Speed Atomic Force Microscopy.ACS nano · 2025Article
- RNA fine-tunes estrogen receptor-alpha binding on low-affinity DNA motifs for transcriptional regulation.The EMBO journal · 2024Article
- Dysregulation of transcriptional condensates in human disease: mechanisms, biological functions, and open questions.Current opinion in genetics & development · 2024Review
- The Blueprint of Logical Decisions in a NF-κB Signaling System.ACS omega · 2024Article
- Transcription decouples estrogen-dependent changes in enhancer-promoter contact frequencies and spatial proximity.PLoS genetics · 2024Article
- Article
- Emerging insights into transcriptional condensates.Experimental & molecular medicine · 2024Review
- Mechanosensitive super-enhancers regulate genes linked to atherosclerosis in endothelial cells.The Journal of cell biology · 2024Article
- A distant global control region is essential for normal expression of anterior HOXA genes during mouse and human craniofacial development.Nature communications · 2024Article
- Transcription factor condensates and signaling driven transcription.Nucleus (Austin, Tex.) · 2023Review
- Phase-separation: a possible new layer for transcriptional regulation by glucocorticoid receptor.Frontiers in endocrinology · 2023Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Unliganded Estrogen receptor alpha (ERα) has been implicated in ligand-dependent gene regulation. Upon ligand exposure, ERα binds to several EREs relatively proximal to the pre-marked, unliganded ERα-bound sites and affects transient but robust gene expression. However, the underlying mechanisms are not fully understood. Here we demonstrate that upon ligand stimulation, persistent sites interact extensively, via chromatin looping, with the proximal transiently ERα-bound sites, forming Ligand Dependent ERα Enhancer Cluster in 3D (LDEC). The E2-target genes are regulated by these clustered enhancers but not by the H3K27Ac super-enhancers. Further, CRISPR-based deletion of TFF1 persistent site disrupts the formation of its LDEC resulting in the loss of E2-dependent expression of TFF1 and its neighboring genes within the same TAD. The LDEC overlap with nuclear ERα condensates that coalesce in a ligand and persistent site dependent manner. Furthermore, formation of clustered enhancers, as well as condensates, coincide with the active phase of signaling and their later disappearance results in the loss of gene expression even though persistent sites remain bound by ERα. Our results establish, at TFF1 and NRIP1 locus, a direct link between ERα condensates, ERα enhancer clusters, and transient, but robust, gene expression in a ligand-dependent fashion.
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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.