ArticleCancer discovery2022
KAT6A and ENL Form an Epigenetic Transcriptional Control Module to Drive Critical Leukemogenic Gene-Expression Programs.
Article in Cancer discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 91 citations in OpenAlex.
- Chidamide, a Histone Deacetylase Inhibitor, Combined With R-GemOx in Relapsed/Refractory Diffuse Large B-Cell Lymphoma (TRUST): A Multicenter, Single-Arm, Phase 2 Trial.Cancer medicine · 2025Trial
- Dynamic regulation of H3K9 modifications in cancer: pathogenesis and targeted therapies.Biomarker research · 2026Review
- Matrix stiffness-induced YEATS2 drives HCC progression via epigenetic activation of the TGFBR2-TAZ-AKT pathway.Cell death and differentiation · 2026Article
- Histone Post-Translational Modifications Regulating Ferroptosis: The Molecular Mechanisms and Disease Associations.Cell biochemistry and function · 2026Review
- CRISPR application in hematological disorders: from bench to bedside.Blood advances · 2026Review
- Hierarchical small molecule inhibition of MYST acetyltransferases.Nature communications · 2026Article
- A Perturb-seq map of a differentiation hub reveals synergistic vulnerabilities in KMT2A-rearranged acute myeloid leukemia.Leukemia · 2026Article
- Lysine Acetyltransferase 6A Drives M1 Macrophage Polarization Through Metabolic Reprogramming in Sepsis-Induced Acute Lung Injury.Biomolecules · 2026Article
- chromIDEAS reveals epigenetic dynamics via multi-dimensional clustering of chromatin states.Nucleic acids research · 2026Article
- PRC2 loss impairs small cell lung cancer tumorigenesis and enhances sensitivity to G9a/GLP inhibition.Communications biology · 2026Article
- Biological Activity and Structural Biology of Current KAT6A Inhibitor Chemotypes.Journal of medicinal chemistry · 2026Article
- KAT6A regulates osteoclast differentiation and bone resorption through TET1-mediated TRPV4 expression.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Construction and Validation of an N7-Methylguanosine-Related Prognostic Model for Acute Myeloid Leukemia.Blood and lymphatic cancer : targets and therapy · 2026Article
- Epigenetic alterations in Myeloid Malignancies.Advances in experimental medicine and biology · 2026Review
- DC-STAMP activates the PI3K/AKT/mTOR signaling pathway to regulate PANoptosis in acute myeloid leukemia.PloS one · 2026Article
- Histone acetyltransferase KAT6A contributes to colon cancer malignant progression by inhibiting ferroptosis.BMC cancer · 2025Article
- Integrative multi-omic analysis identifies key transcription factors and target proteins in renal cell carcinoma and its subtypes.bioRxiv : the preprint server for biology · 2025Article
- KAT6A acetyltransferase accelerates colorectal cancer progression through upregulating BRD1 protein expression via acetylation modification.Cancer cell international · 2025Article
- Combinatorial inhibition of LSD1 and Menin induces therapeutic differentiation in AML.bioRxiv : the preprint server for biology · 2025Article
- Chromatin Regulatory Targets for Anticancer Therapeutics.Chemical reviews · 2025Review
7 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors at 5 institutions in 4 countries.
Funding
Abstract
Epigenetic programs are dysregulated in acute myeloid leukemia (AML) and help enforce an oncogenic state of differentiation arrest. To identify key epigenetic regulators of AML cell fate, we performed a differentiation-focused CRISPR screen in AML cells. This screen identified the histone acetyltransferase KAT6A as a novel regulator of myeloid differentiation that drives critical leukemogenic gene-expression programs. We show that KAT6A is the initiator of a newly described transcriptional control module in which KAT6A-catalyzed promoter H3K9ac is bound by the acetyl-lysine reader ENL, which in turn cooperates with a network of chromatin factors to induce transcriptional elongation. Inhibition of KAT6A has strong anti-AML phenotypes in vitro and in vivo, suggesting that KAT6A small-molecule inhibitors could be of high therapeutic interest for mono-therapy or combinatorial differentiation-based treatment of AML. SIGNIFICANCE: AML is a poor-prognosis disease characterized by differentiation blockade. Through a cell-fate CRISPR screen, we identified KAT6A as a novel regulator of AML cell differentiation. Mechanistically, KAT6A cooperates with ENL in a "writer-reader" epigenetic transcriptional control module. These results uncover a new epigenetic dependency and therapeutic opportunity in AML. This article is highlighted in the In This Issue feature, p. 587.
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