ArticleNature communications2024
KAT8-mediated H4K16ac is essential for sustaining trophoblast self-renewal and proliferation via regulating CDX2.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- CHD8-Dependent Chromatin Licensing Sustains Trophoblast Stem Cell Transcriptional Programs.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- KAT8-mediated epigenetic modifications: Physiological functions, heterogeneity in disease, and advances in targeted development.iScience · 2026Review
- The KAT8-CDK1 K33 acetylation axis drives doxorubicin resistance by suppressing ferroptosis and apoptosis in breast cancer.Cell death & disease · 2026Article
- Chromatin chronicles: Unlocking the therapeutic potential of histone modifiers in hepatocellular carcinoma.Medical oncology (Northwood, London, England) · 2026Review
- Lysine acetyltransferase 8-mediated histone acetylation, regulated by GBA1, is associated with lysosomal function related to α-Synuclein pathology.Cell death & disease · 2026Article
- Asperosaponin VI Ameliorates Spontaneous Abortion by Inhibiting Trophoblast Ferroptosis via the KEAP1/NRF2/GPX4 Axis.Antioxidants (Basel, Switzerland) · 2026Article
- Lactate metabolism and lactylation in cancer: from pathogenesis to therapeutic advances.Signal transduction and targeted therapy · 2026Review
- Characterization and regulatory mechanism evaluation of C8orf33 in hepatocellular carcinoma through multiomics profiling.Discover oncology · 2026Article
- MOF-mediated H4K16ac is critical for blastocyst formation in sheep by shaping promoter accessibility and transcription.Communications biology · 2026Article
- Review
- Interrogating the regulatory epigenome of cellular senescence.Cellular and molecular life sciences : CMLS · 2025Review
- Fto-mediated mJournal of biomedical science · 2025Article
- A comprehensive review of histone modifications during mammalian oogenesis and early embryo development.Histochemistry and cell biology · 2025Review
- Abnormal lineage differentiation of peri-implantation aneuploid embryos revealed by single-cell RNA sequencing.Clinical and translational medicine · 2025Article
- Elevated NGF provokes decidual lipid peroxidation and promotes preterm birth in mice.Journal of translational medicine · 2025Article
- Gastrodin attenuates rheumatoid arthritis by targeting KAT8 to inhibit the lactylation of H3K9.Frontiers in pharmacology · 2025Article
- Epigenetics of maternal-fetal interface immune microenvironment and placental related pregnancy complications.Frontiers in immunology · 2025Review
- Article
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Authors and funding
21 authors.
Funding
Abstract
Abnormal trophoblast self-renewal and differentiation during early gestation is the major cause of miscarriage, yet the underlying regulatory mechanisms remain elusive. Here, we show that trophoblast specific deletion of Kat8, a MYST family histone acetyltransferase, leads to extraembryonic ectoderm abnormalities and embryonic lethality. Employing RNA-seq and CUT&Tag analyses on trophoblast stem cells (TSCs), we further discover that KAT8 regulates the transcriptional activation of the trophoblast stemness marker, CDX2, via acetylating H4K16. Remarkably, CDX2 overexpression partially rescues the defects arising from Kat8 knockout. Moreover, increasing H4K16ac via using deacetylase SIRT1 inhibitor, EX527, restores CDX2 levels and promoted placental development. Clinical analysis shows reduced KAT8, CDX2 and H4K16ac expression are associated with recurrent pregnancy loss (RPL). Trophoblast organoids derived from these patients exhibit impaired TSC self-renewal and growth, which are significantly ameliorated with EX527 treatment. These findings suggest the therapeutic potential of targeting the KAT8-H4K16ac-CDX2 axis for mitigating RPL, shedding light on early gestational abnormalities.
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