ArticleNucleic acids research2022
A histidine cluster determines YY1-compartmentalized coactivators and chromatin elements in phase-separated enhancer clusters.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 87 citations in OpenAlex.
- hnRNPK condensates facilitate enhancer-promoter looping and RNA polymerase II recruitment.Nature genetics · 2026Article
- Review
- G-Quadruplexes: Structural Diversity and Emerging Roles in Biomolecular Condensation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Exploring the GM-CSF histidine triad as a modulator of structure, molecular motion, and ligand binding.RSC chemical biology · 2026Article
- YY1 in hematopoietic stem cells: epigenetic regulation, chromatin architecture, and aging.Current opinion in hematology · 2026Review
- Polyphosphate as a novel regulator of super-enhancer complexes: disruption of phase separation and gene expression.Nucleic acids research · 2026Article
- YY1 Interacts with Promoter R-Loops to Regulate Transcription.Journal of the American Chemical Society · 2026Article
- JMJD2 regulates enhancer-promoter interactions via biomolecular condensate formation.Nature genetics · 2026Article
- Regulation of transcription by R loop-nucleated transcription condensate assembly.Cell & bioscience · 2026Review
- Super-enhancer-driven core transcription factor FOXP1 delays endothelial cell senescence via phase separation-mediated SESN3 activation.Theranostics · 2026Article
- RNA polymerase II transcription compartments - from factories to condensates.Nature reviews. Genetics · 2025Review
- Proteins driving liquid-liquid phase separation and histone modifications cooperatively associate with chromatin looping and transcriptional regulation.Epigenetics & chromatin · 2025Article
- Specificity in clustering of gene-specific transcription factors is encoded in the genome.Nucleic acids research · 2025Article
- YY1 enhances HIF-1α stability in tumor-associated macrophages to suppress anti-tumor immunity of prostate cancer in mice.Nature communications · 2025Article
- Klf5-adjacent super-enhancer functions as a 3D genome structure-dependent transcriptional driver to safeguard ESC identity.Nature communications · 2025Article
- Host factor RBM25 promotes HBV replication through Yin Yang 1-mediated cccDNA transcription.Virologica Sinica · 2025Article
- Upregulation of YY1 in M2 macrophages promotes secretion of exosomes containing hsa-circ-0000326 via super-enhancers to facilitate prostate cancer progression.Molecular and cellular biochemistry · 2025Article
- Phase Separation in Chromatin Organization and Human Diseases.International journal of molecular sciences · 2025Review
- Endoplasmic reticulum stress related super-enhancers suppress cuproptosis via glycolysis reprogramming in lung adenocarcinoma.Cell death & disease · 2025Article
- Predicting gene expression changes from chromatin structure modification.NPJ systems biology and applications · 2025Article
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
As an oncogenic transcription factor, Yin Yang 1 (YY1) regulates enhancer and promoter connection. However, gaps still exist in understanding how YY1 coordinates coactivators and chromatin enhancer elements to assemble enhancers and super-enhancers. Here, we demonstrate that a histidine cluster in YY1's transactivation domain is essential for its formation of phase separation condensates, which can be extended to additional proteins. The histidine cluster is also required for YY1-promoted cell proliferation, migration, clonogenicity and tumor growth. YY1-rich nuclear puncta contain coactivators EP300, BRD4, MED1 and active RNA polymerase II, and colocalize with histone markers of gene activation, but not that of repression. Furthermore, YY1 binds to the consensus motifs in the FOXM1 promoter to activate its expression. Wild-type YY1, but not its phase separation defective mutant, connects multiple enhancer elements and the FOXM1 promoter to form an enhancer cluster. Consistently, fluorescent in situ hybridization (FISH) assays reveal the colocalization of YY1 puncta with both the FOXM1 gene locus and its nascent RNA transcript. Overall, this study demonstrates that YY1 activates target gene expression through forming liquid-liquid phase separation condensates to compartmentalize both coactivators and enhancer elements, and the histidine cluster of YY1 plays a determinant role in this regulatory mechanism.
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