ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
ACSS2-Mediated Histone H4 Lysine 12 Crotonylation (H4K12cr) Alleviates Colitis via Enhancing Transcription of CLDN7.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Acetoacetate-GPR43 axis epigenetically silences IL-6/CSF1 to restrict TAMs-driven metastatic lung cancer.Journal of translational medicine · 2026Article
- Coming to light: the transcriptional regulatory roles of histone lysine crotonylation in health and disease.Cellular & molecular biology letters · 2026Review
- CLDN7: Epithelial gatekeeper from physiology to pathology‑roles in cancer and epithelial‑related diseases (Review).International journal of molecular medicine · 2026Review
- Glutamine-mediated crosstalk between M2 macrophages and tumor cells via the SLC38A5/FOXM1/CNIH4 axis promotes oral squamous cell carcinoma progression.Journal of translational medicine · 2026Article
- Shared immune dysregulation in systemic lupus erythematosus and colorectal cancer: a multi-omics guided discovery of DNASE1L3-centric efferocytosis deficiency.Frontiers in immunology · 2026Article
- Occupational silica exposure drives systemic immune dysregulation and tumor microenvironment susceptibility: evidence from a real-world study.Frontiers in immunology · 2026Article
- A transcriptome-defined TAM-rich phenotype identifies a macrophage-enriched, hypoxia-linked immune contexture in glioblastoma: multi-cohort transcriptomic validation and local histopathological correlation.Frontiers in immunology · 2026Article
- UBTD1 Drives Ovarian Cancer Progression via Mutation-Associated Alterations, Stromal Microenvironment Remodeling, and TNF/AP-1 Signaling.Human mutation · 2026Article
- Frontier research and clinical application prospects of microbiome biomarkers in autoimmune diseases.Frontiers in immunology · 2026Review
- Microbial metabolic memory in inflammatory bowel disease: microbiota-derived metabolites, host-microbe reprogramming, and relapse susceptibility.Frontiers in microbiology · 2026Review
- ACSS2-Mediated Histone H4 Lysine 12 Crotonylation (H4K12cr) Alleviates Colitis via Enhancing Transcription of CLDN7.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
Histone lysine crotonylation (Kcr), a highly conserved posttranslational modification, plays critical roles in various biological processes. Nevertheless, the dynamic alterations and functions of histone Kcr in inflammatory bowel disease (IBD) remain poorly explored. Herein, a notable decrease of both Pan-Kcr and ACSS2 (acyl-CoA synthetase short-chain family member 2), the key enzyme for crotonyl-CoA generation, is revealed in inflamed intestinal epithelial cells. Genetic or pharmacological inhibition of ACSS2 dramatically impairs mouse intestinal barrier integrity and exacerbates colitis. Mechanistically, ACSS2-mediated histone H4 lysine 12 crotonylation (H4K12cr) upregulates CLDN7 expression to fortify intestinal epithelial barrier, which can be augmented by crotonate supplementation. Furthermore, tumor necrosis factor-α (TNF-α) is revealed to enhance the m6A modification of ACSS2 mRNA, consequently destabilizing and downregulating ACSS2. Combinational therapy involving anti-TNF-α and crotonate can significantly ameliorate colitis. Overall, ACSS2-mediated H4K12cr emerges as a pivotal modulator governing intestinal barrier function during IBD progression.
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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 Socratic graph.