{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n KAT8 (also known as MOF or hMOF) is a highly conserved member of the MYST family of histone acetyltransferases that primarily catalyzes acetylation of histone H4 at lysine 16 (H4K16Ac), a modification critical for establishing open chromatin and regulating gene expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition to its canonical role in modifying nucleosomal histones, KAT8 participates in the acetylation of non‐histone proteins such as p53—thereby influencing cell fate decisions like apoptosis—and is essential for orchestrating a proper cellular response to DNA damage by facilitating the recruitment of repair factors and modulating the activity of key signaling proteins."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n KAT8’s function is largely executed via its incorporation into multi‐subunit complexes such as the MSL and NSL assemblies, which direct its substrate specificity and link its enzymatic activity to diverse cellular contexts including embryonic development, maintenance of pluripotency, and proper dosage compensation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, KAT8 function is dynamically regulated through autoacetylation and by interplay with other modulators such as SIRT1 and PTEN, which fine‐tune its activity in response to cellular stresses. Such regulation is critical not only for the maintenance of genome integrity—by ensuring appropriate DNA damage repair and checkpoint control—but also for modulating autophagy and mitochondrial gene expression to adapt to metabolic demands."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "10"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Dysregulation of KAT8 has been implicated in oncogenesis, with altered expression or mislocalization correlating with aberrant chromatin architecture, defective transcription, impaired DNA repair, and ultimately tumor progression. In several cancers, reduced H4K16 acetylation—reflecting compromised KAT8 activity—serves as an epigenetic hallmark and prognostic marker, while KAT8-mediated acetylation of factors such as p53 and Nrf2 influences cell survival and resistance to therapy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, structural studies of KAT8 within its complexes have provided insights into its catalytic mechanism and partners that mediate chromatin targeting, while genome-wide analyses have linked KAT8-dependent H4K16 acetylation to the regulation of RNA polymerase II pausing and transcriptional elongation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": " Collectively, these findings underscore the multifaceted role of KAT8 as a central integrator of epigenetic signals that govern chromatin architecture, gene expression, DNA repair, and cellular homeostasis.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Stephen M Sykes, Hestia S Mellert, Marc A Holbert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Acetylation of the p53 DNA-binding domain regulates apoptosis induction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2006.11.026"}], "href": "https://doi.org/10.1016/j.molcel.2006.11.026"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17189187"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17189187"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Mikko Taipale, Stephen Rea, Karsten Richter, et al. "}, {"type": "b", "children": [{"type": "t", "text": "hMOF histone acetyltransferase is required for histone H4 lysine 16 acetylation in mammalian cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.25.15.6798-6810.2005"}], "href": "https://doi.org/10.1128/MCB.25.15.6798-6810.2005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16024812"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16024812"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Arun Gupta, Girdhar G Sharma, Charles S H Young, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Involvement of human MOF in ATM function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.25.12.5292-5305.2005"}], "href": "https://doi.org/10.1128/MCB.25.12.5292-5305.2005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15923642"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15923642"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yong Cai, Jingji Jin, Selene K Swanson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Subunit composition and substrate specificity of a MOF-containing histone acetyltransferase distinct from the male-specific lethal (MSL) complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.C109.087981"}], "href": "https://doi.org/10.1074/jbc.C109.087981"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20018852"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20018852"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Arun Gupta, T Geraldine Guerin-Peyrou, Girdhar G Sharma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The mammalian ortholog of Drosophila MOF that acetylates histone H4 lysine 16 is essential for embryogenesis and oncogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.01045-07"}], "href": "https://doi.org/10.1128/MCB.01045-07"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17967868"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17967868"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Tim Thomas, Mathew P Dixon, Andrew J Kueh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mof (MYST1 or KAT8) is essential for progression of embryonic development past the blastocyst stage and required for normal chromatin architecture."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.02202-07"}], "href": "https://doi.org/10.1128/MCB.02202-07"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18541669"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18541669"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Tomasz Chelmicki, Friederike Dündar, Matthew James Turley, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MOF-associated complexes ensure stem cell identity and Xist repression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.02024"}], "href": "https://doi.org/10.7554/eLife.02024"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24842875"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24842875"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Lirong Peng, Hongbo Ling, Zhigang Yuan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SIRT1 negatively regulates the activities, functions, and protein levels of hMOF and TIP60."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00496-12"}], "href": "https://doi.org/10.1128/MCB.00496-12"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22586264"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22586264"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Aindrila Chatterjee, Janine Seyfferth, Jacopo Lucci, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MOF Acetyl Transferase Regulates Transcription and Respiration in Mitochondria."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2016.09.052"}], "href": "https://doi.org/10.1016/j.cell.2016.09.052"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27768893"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27768893"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Zhu Hong Chen, Minglu Zhu, Jingyi Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PTEN interacts with histone H1 and controls chromatin condensation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2014.08.008"}], "href": "https://doi.org/10.1016/j.celrep.2014.08.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25199838"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25199838"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Stefan Pfister, Stephen Rea, Mikko Taipale, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The histone acetyltransferase hMOF is frequently downregulated in primary breast carcinoma and medulloblastoma and constitutes a biomarker for clinical outcome in medulloblastoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Cancer (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ijc.23283"}], "href": "https://doi.org/10.1002/ijc.23283"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18058815"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18058815"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Zhiwei Chen, Xiangyun Ye, Naiwang Tang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The histone acetylranseferase hMOF acetylates Nrf2 and regulates anti-drug responses in human non-small cell lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Br J Pharmacol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/bph.12661"}], "href": "https://doi.org/10.1111/bph.12661"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24571482"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24571482"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Jan Kadlec, Erinc Hallacli, Michael Lipp, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural basis for MOF and MSL3 recruitment into the dosage compensation complex by MSL1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Struct Mol Biol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nsmb.1960"}], "href": "https://doi.org/10.1038/nsmb.1960"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21217699"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21217699"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Priya Kapoor-Vazirani, Jacob D Kagey, Paula M Vertino "}, {"type": "b", "children": [{"type": "t", "text": "SUV420H2-mediated H4K20 trimethylation enforces RNA polymerase II promoter-proximal pausing by blocking hMOF-dependent H4K16 acetylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00524-10"}], "href": "https://doi.org/10.1128/MCB.00524-10"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21321083"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21321083"}]}]}]}