ArticleGastroenterology2026
Chemical Perturbations Impacting Histone Acetylation Govern Colorectal Cancer Differentiation.
Article in Gastroenterology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
5 citing papers in PubMed.
- Targeting the Epigenome in Colorectal Cancer.International journal of molecular sciences · 2026Review
- PIK3CA Mutations Downregulate PPT1 to Promote Adipogenesis by Suppressing P300 Depalmitoylation and Phase Separation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Unraveling the complexity of the histone code: implications for gene regulation and disease.Genome biology · 2026Review
- Oncofetal reprogramming and cellular plasticity in colorectal cancer: from mechanisms to clinical translation.Frontiers in oncology · 2026Review
- Metastasis-Specific Biomarker SPP1 and its Characterization in Colorectal Cancer with HIV Infection.Current HIV research · 2026Article
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Authors and funding
20 authors.
Funding
Abstract
BACKGROUND &
aimsAberrant epigenetic programs that suppress differentiation and enhance plasticity drive colorectal cancer (CRC), yet the molecular determinants underlying these processes remain elusive. We aimed to identify and characterize epigenetic regulators of CRC differentiation, uncovering mechanisms that reprogram cancer cell states.
methodsA small-molecule library targeting epigenetic regulators was screened using an endogenous dual-reporter system. We evaluated lead compounds in mouse and human CRC models via histopathology, cellular assays, epigenetic studies, mass spectrometry-based histone modification profiling, and single-cell RNA sequencing. Integrative analyses of drug-induced chromatin dynamics, gene expression, target engagement, and histone marks elucidated molecular mechanisms. Focused genetic screens were conducted to identify regulators of histone deacetylase (HDAC)1/2-mediated differentiation.
resultsWe found that inhibition of the HDAC1/2 catalytic domain promotes CRC differentiation and suppresses tumor growth. Unbiased profiling of histone modifications identified acetylation of lysine 27 on histone H3 protein subunit (H3K27ac) and acetylation of lysine 9 on histone H3 protein subunit (H3K9ac) as critical regulatory marks, with genome-wide analyses demonstrating their enrichment at HDAC1/2-bound regions associated with open chromatin and up-regulated differentiation genes. Disrupting H3K27ac by targeted degradation of acetyltransferase E1A binding protein P300 reversed the differentiation phenotype induced by HDAC1/2 inhibition in a patient-derived CRC organoid. Genetic screens revealed that death-associated protein kinase 3 contributes to H3K27ac-mediated CRC differentiation induced by HDAC1/2 inhibition.
conclusionsOur findings establish histone acetylation as a chemically targetable mechanism governing CRC cell fate and demonstrate that epigenetic reprogramming can be leveraged as a therapeutic strategy. By identifying HDAC1/2 inhibition as a driver of differentiation and revealing H3K27ac as a key regulatory mark, this study provides a framework for targeting chromatin-modifying enzymes to counteract CRC plasticity and improve treatment outcomes.
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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 Socratic graph.