Ask about this productRelated genes to: MYST2 antibody
- Gene:
- KAT7 NIH gene
- Name:
- lysine acetyltransferase 7
- Previous symbol:
- MYST2
- Synonyms:
- HBOA, HBO1, ZC2HC7
- Chromosome:
- 17q21.33
- Locus Type:
- gene with protein product
- Date approved:
- 2003-06-03
- Date modifiied:
- 2016-10-05
Related products to: MYST2 antibody
Related articles to: MYST2 antibody
- The INhibitor of Growth (ING) proteins are plant homeodomain (PHD) zinc-finger epigenetic readers that recognize trimethylated lysine 4 of histone H3 (H3K4me3) and couple it to lysine-acetyltransferase (KAT) or -deacetylase (KDAC) activity on chromatin. ING4 and ING5 are among the family's closest paralogs, which share a four-domain architecture and high sequence identity, with divergence concentrated outside the PHD finger. Earlier reviews focused either on the family as a whole or on the individual INGs. This paper is the first to directly compare ING4 and ING5, including their structures, functions within KAT complexes, and roles in cancer and development, noting where they overlap and diverge. Either paralog can occupy the ING position in HBO1 (KAT7) complexes, whereas only ING5 is found in MOZ and MORF (KAT6A/B) complexes. In cancers, ING4 and ING5 generally act as tumor suppressors but can also promote malignancy and stemness. The bulk of evidence for mechanistically explaining the effects of ING4/5 in cancers comes from ectopic overexpression studies. In differentiation, ING5 has been investigated far more than ING4, and the roles of the two mostly diverge: ING5 participates in maintaining stemness in neural, epidermal, and brain tumor initiating cell lines, as well as proliferation of mesenchymal stem cells, whereas ING4 was found to restrain hematopoietic stem cell self-renewal, promote prostate epithelial differentiation, but promote stemness of renal cell carcinoma cells. They nonetheless compensate for one another in embryonic survival, since either paralog alone prevents the arrest seen in double knockouts. The key remaining questions include what determines the structural basis of ING5's MOZ/MORF selectivity, what the precise conditions are under which they substitute for one another, how exactly ING4 and ING5 can be targeted in cancer therapy, and whether the roles of the two paralogs are conserved across species. - Source: PubMed
Publication date: 2026/07/27
Dadoyan SergeyBartizal Tom JAmarsingha SakunikaRiabowol Karl - Pelvic organ prolapse (POP) is a common gynecological disorder severely affecting quality of life, characterized by extracellular matrix (ECM) disruption and metabolic dysregulation. Lactylation is a lactate-induced post-translational modification that regulates gene expression, but its role in POP remains unclear. Here, we demonstrate that enhanced glycolysis and lactate accumulation drive histone lactylation, which impairs mitochondrial function and collagen biosynthesis in POP. Furthermore, we identify histone acetyltransferase Kat7 as a key lactyltransferase that catalyzes H3K14 and H3K18 lactylation via its glutamate residue E508. Notably, H3K14la/H3K18la suppresses the expression of Slc25a51, a mitochondrial NAD transporter, leading to NAD deficiency, hyperacetylation of P5CS, proline depletion, and inhibition of fibroblast proliferation. In vivo, inhibition of glycolysis or Kat7 activity ameliorates vaginal distension-induced lactylation, restores Slc25a51 expression, and improves collagen deposition. Taken together, these findings reveal that histone lactylation disrupts mitochondrial NAD homeostasis and proline metabolism in fibroblasts, thus inhibiting collagen synthesis and enhancing POP pathogenesis. We show that histone H3 lactylation at K14 and K18 promotes POP progression. Kat7 catalyzes lactylation of histone H3 at K14 and K18, and this modification represses Slc25a51 expression, disrupts mitochondrial NAD transport, and inhibits proline-dependent collagen synthesis. Targeting lactate production or Kat7 may restore mitochondrial function and ECM homeostasis, providing a potential treatment for POP. - Source: PubMed
Publication date: 2026/07/23
He YongLiu ChengLi BingshuHong ShashaTang JianmingHuang GuotaoYang LianChen MaoZhang ShufeiXiao YaLiu JianfengNing MinqiJiang NuoXiang ChunrongHuang ShouqiHong Li - Skeletal muscle differentiation depends on precise temporal regulation of protein modifications. To define how phosphorylation and lysine acetylation change during this process, we applied tandem mass tag (TMT)-based quantitative proteomics to human myoblasts sampled at six stages spanning proliferation, induction of differentiation, and early myotube formation. Using sequential enrichment of phosphorylated and acetylated peptides, high-pH fractionation, and high-resolution mass spectrometry, we identified more than 22,000 modified peptides and quantified their temporal behavior after correction for protein abundance. Phosphorylation exhibited extensive site-specific remodeling throughout the time course, whereas acetylation showed a pronounced relative increase during late differentiation. Integration of corrected modification levels with protein abundances and temporal clustering revealed stage-specific regulation of processes linked to cell-cycle withdrawal, metabolic transitions, cytoskeletal reorganization, and chromatin-associated functions. Predicted temporal activity profiles of kinases, acetyltransferases, and deacetylases uncovered coordinated regulatory patterns, including activity relationships involving CK2A1-HDAC1/2, PRKAA1-HAT1, and CDK1/2-KAT7. Dual-modified proteins such as lamin A/C and glycolytic enzymes displayed densely regulated clusters of phosphorylation and acetylation sites that may contribute to nuclear remodeling and metabolic adaptation during myogenesis. Together, this work provides a high-resolution temporal phospho-acetylome atlas of human muscle cell differentiation, identifies candidate phosphorylation-acetylation coordination patterns, and establishes a systems-level resource for future mechanistic studies of post-translational regulation in skeletal muscle development. - Source: PubMed
Publication date: 2026/07/02
Smith Lauren EHagensen Christina ETsiamis Vasileiosvan Waardenberg Ashley JMamchaoui KamelJensen Ole NSchwämmle VeitRogowska-Wrzesinska Adelina - Centromeres are specialized chromatin structures essential for equal chromosome segregation. The human centromeres are organized on a portion of homogeneously repeated DNA sequence and contains nucleosomes including centromere specific histone H3 variant CENP-A. Histone modifications around the CENP-A dense region are also thought to have important roles in centromere function. Here, we used human artificial chromosome (HAC) system based on synthetic centromeric repeat DNA to enable structural and chromatin analysis at ∼2-kb resolution within defined centromere core domains. Analysis using this HAC centromere showed that the CENP-A dense regions span approximately 18-50 kb in size and coexisted with euchromatic histone modifications in an interdependent manner. We further found that when DNA replication reduced CENP-A density, a heterochromatin modification H3K9me3 transiently accumulated in the CENP-A-dense regions. This accumulation was suppressed by the CENP-A deposition factor HJURP and the histone acetyltransferase KAT7, suggesting that CENP-A assembly and euchromatic modifications interdependently antagonize heterochromatin accumulation. The synthetic centromere DNA generated in this study elucidates the epigenetic landscape within the centromere core regions and provides a more precise framework for understanding the dynamic balance between CENP-A assembly and histone modifications. - Source: PubMed
Ohzeki JunichiroWatanabe AkikoLee Jia XianMinami ChiharuKugou KazutoYamazaki KyotaroShirasawa KentaIsobe SachikoEndo YusukeKazuki Yasuhiro - NPM1 mutation (NPM1c)-driven acute myeloid leukemia (AML) is characterized by the sequestration of nuclear proteins and chromatin hijacking. Current treatment strategies targeting NPM1c AML are often indirect, which might lead to toxicity and resistance. In this study, we developed an allele-specific siRNA that selectively silences NPM1c while preserving the function of wild-type NPM1. This approach inhibited proliferation and promoted myeloid differentiation in NPM1-mutated AML cells in vitro. Notably, the systemic delivery of chemically optimized siNPM1c via lipid nanoparticles (LNPs) significantly reduced leukemogenesis, and enhanced the therapeutic efficacy of the menin inhibitor revumenib and overcame its resistance in vivo. Mechanistically, NPM1c recruits KAT7 and p300, driving leukemogenic transcription and establishing a pathogenic acetylome and open chromatin state. KAT7 recruitment is crucial for the retention of this complex on chromatin. Targeting NPM1c with siRNA disrupts this interaction, reverses the oncogenic epigenetic landscape, and suppresses transcription. Our findings demonstrate that silencing NPM1c effectively suppresses AML by dismantling a pathogenic KAT7/p300-dependent acetylome, highlighting the potential of LNP‑delivered siNPM1c as a promising therapeutic strategy, either as a monotherapy or in combination with menin inhibition. - Source: PubMed
Publication date: 2026/06/26
Hou YongqiangXing YunzhiChen ChunjieSu DongxueZhou ZhienYe YiLai ZhangjianPeng ZhixianCai HongxiSun MinLiu YueYang BingyingHuang HaitaoLi ZheLi JinhuanLi JunhongGao HuanLi JiaxinZhao HaoShi YiranChen QinghuaLong JunHu JiongZhou DawangChen Lanfen