ArticleNature chemical biology2019
Bromodomain inhibition of the coactivators CBP/EP300 facilitate cellular reprogramming.
Article in Nature chemical biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 99 citations in OpenAlex.
- Eyes Toward the Clinic: Selective Inhibition and Degradation Approaches to Bromodomain-Containing Proteins.Chembiochem : a European journal of chemical biology · 2026Review
- KMT2C Loss Promotes NF2-Wildtype Meningioma Progression and Ferroptosis Sensitivity via Epigenetic Repression of Hippo Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- AP-1 mediates cellular adaptation and memory formation.Nature communications · 2026Article
- Integrated Single-Cell analysis Reveals molecular correlation of maternal-to-zygotic transition between human and pig embryo.Journal of translational medicine · 2026Article
- Enhancer RNA-mediated transcriptional regulation of TDP-43 during early neural lineage specification.Animal cells and systems · 2026Article
- Human iPSCs derived from cryopreserved testicular somatic cells enable germline regeneration in childhood cancer survivors.Human reproduction open · 2026Article
- H3K27ac Is Essential for Human Naive Pluripotency Modulated by m6A-Driven EP300 Expression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Therapeutic targeting of the p300/CBP bromodomain enhances the efficacy of immune checkpoint blockade therapy.Oncogene · 2025Article
- A rapid chemical reprogramming system to generate human pluripotent stem cells.Nature chemical biology · 2025Article
- Investigating Müller glia reprogramming in mice: a retrospective of the last decade, and a look to the future.Neural regeneration research · 2025Article
- A chromatin-focused CRISPR screen identifies USP22 as a barrier to somatic cell reprogramming.Communications biology · 2025Article
- Scaffolding Activities of Pseudodeacetylase HDAC7.ACS chemical biology · 2025Review
- Epigenetic drug screening identifies enzyme inhibitors A-196 and TMP-269 as novel regulators of sprouting angiogenesis.Scientific reports · 2025Article
- Mouse Embryonic Fibroblasts Reprogramming to Induced Pluripotent Stem Cells by T3.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Generation of Bona Fide Human Induced Trophoblast Stem Cells by Direct Reprogramming of Term Umbilical Cord Cells.International journal of molecular sciences · 2024Article
- Chromatin accessibility: biological functions, molecular mechanisms and therapeutic application.Signal transduction and targeted therapy · 2024Review
- EnhancerNet: a predictive model of cell identity dynamics through enhancer selection.Development (Cambridge, England) · 2024Article
- Targeting CBP and p300: Emerging Anticancer Agents.Molecules (Basel, Switzerland) · 2024Review
- Unlocking cellular plasticity: enhancing human iPSC reprogramming through bromodomain inhibition and extracellular matrix gene expression regulation.Stem cells (Dayton, Ohio) · 2024Article
- AP-1 Mediates Cellular Adaptation and Memory Formation During Therapy Resistance.bioRxiv : the preprint server for biology · 2024Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
Silencing of the somatic cell type-specific genes is a critical yet poorly understood step in reprogramming. To uncover pathways that maintain cell identity, we performed a reprogramming screen using inhibitors of chromatin factors. Here, we identify acetyl-lysine competitive inhibitors targeting the bromodomains of coactivators CREB (cyclic-AMP response element binding protein) binding protein (CBP) and E1A binding protein of 300 kDa (EP300) as potent enhancers of reprogramming. These inhibitors accelerate reprogramming, are critical during its early stages and, when combined with DOT1L inhibition, enable efficient derivation of human induced pluripotent stem cells (iPSCs) with OCT4 and SOX2. In contrast, catalytic inhibition of CBP/EP300 prevents iPSC formation, suggesting distinct functions for different coactivator domains in reprogramming. CBP/EP300 bromodomain inhibition decreases somatic-specific gene expression, histone H3 lysine 27 acetylation (H3K27Ac) and chromatin accessibility at target promoters and enhancers. The master mesenchymal transcription factor PRRX1 is one such functionally important target of CBP/EP300 bromodomain inhibition. Collectively, these results show that CBP/EP300 bromodomains sustain cell-type-specific gene expression and maintain cell identity.
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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.