Ask about this productRelated genes to: ASH2L antibody
- Gene:
- ASH2L NIH gene
- Name:
- ASH2 like, histone lysine methyltransferase complex subunit
- Previous symbol:
- ASH2L1
- Synonyms:
- ASH2L2, ASH2, Bre2
- Chromosome:
- 8p11.23
- Locus Type:
- gene with protein product
- Date approved:
- 1998-12-03
- Date modifiied:
- 2018-04-23
Related products to: ASH2L antibody
Related articles to: ASH2L antibody
- Members of the Lysine MethylTransferase 2 (KMT2) family are often abnormally expressed and mutated in many cancers. Similarly, several mutations listed in cancer databases map to key functional regions of KMT2 regulatory subunits, such as WD repeat domain 5 (WDR5), Retinoblastoma binding protein 5 (RbBP5), absent-small-homeotic-2-like (ASH2L), and DumPY-30 (DPY-30). In this study, we report the systematic characterization of cancer-associated mutations that map to regions important for the WDR5/RbBP5/ASH2L/DPY-30 (WRAD) complex formation. Both binding and thermal stability assays show that several cancer-related mutations do not affect ASH2L binding to DPY-30 or RbBP5. A subset of gain-of-function mutants highlights the role of long-range networks of interactions underlying RbBP5 binding by ASH2L. Parallel analysis of RbBP5 mutations shows additional variants that weaken its interactions with WDR5. Finally, systematic mapping of RbBP5 residues interacting with WDR5 defines the optimal WDR5-binding motif and shows that introducing hydrophobic residues beyond the central VDV sequence increases binding affinity. Overall, these findings reveal surprising gain-of-function mutations in ASH2L and provide a framework for targeting this epigenetic hub therapeutically. - Source: PubMed
Grégoire SabrinaChow SaraJoshi MonikaZhang PamelaAhmad Aws AlmirJanna AshleyTremblay VeroniqueMuñoz MarceloMer ArvindCouture Jean-Francois - Nucleomodulins are a class of effector proteins secreted by bacterial pathogens that translocate into the host cell nucleus to modulate nuclear processes. However, their target proteins and underlying molecular mechanisms remain poorly understood in mycobacteria. Herein, we identified a conserved hypothetical protein Rv1075c, designated MgdE, as a nucleomodulin that enhances mycobacterial intracellular survival. MgdE undergoes nuclear translocation via two nuclear localization signals, KRIR and RLRRPR, and interacts with ASH2L and WDR5, two subunits of the host histone methyltransferase COMPASS complex. This interaction suppresses histone H3 lysine 4 (H3K4) methylation-mediated transcription of pro-inflammatory genes, including and , thereby promoting mycobacterial survival in both macrophages and mice. Our study provides the first experimental evidence that a bacterial nucleomodulin facilitates intracellular survival by directly targeting the host COMPASS complex. These findings advance our understanding of mycobacterial pathogenesis by revealing a novel mechanism that contributes to its intracellular survival strategy. - Source: PubMed
Publication date: 2026/03/31
Chen LiuDuan BaojieChen PingpingJiang QiangWang YifanLu LuChen YingyuHu ChangminZhang LeiGuo Aizhen - Histone H3 lysine 4 methylation (H3K4me) is generally associated with active transcription and bivalent chromatin but can also contribute to repression. In metazoans, H3K4 methylation is catalysed by KMT2 methyltransferases assembled with the core scaffolding proteins WDR5, ASH2L, and RBBP5. RBBP5 mediates complex assembly and nucleosome binding, whilst WDR5 stabilises interactions to promote tri-methylation. However, WDR5 also exhibits additional moonlighting functions, leaving its specific roles in H3K4 methylation and transcription regulation unclear. Using C. elegans embryos, spike-in ChIP-seq, and null alleles of wdr-5(-) and rbbp-5(-), we dissected the contributions of these scaffolds towards H3K4 mono-, di-, and tri-methylation as well as gene expression during C. elegans embryogenesis. - Source: PubMed
Publication date: 2026/03/25
Samsudin Nurulhafizah BintiWang SiyaoFisher KatePoulin Gino B - Epigenetic regulation plays a pivotal role in adipocyte development and thermogenesis. Ash2l, a key component of the COMPASS (Complex of Proteins Associated with Set1) histone methyltransferase, regulates gene expression through epigenetic mechanisms. This study explored the role of Ash2l in adipose tissue thermogenesis and obesity-related metabolic dysfunction. - Source: PubMed
Publication date: 2026/03/23
Hu YajieZhao JialinXiao ChenxiLiu JiayaoXu JieXu ShenhanZhong WenChen RuoxueHe MengtingFan ChunxiangChang JunLiu Xinhua - The ASH2L-DPY30 interaction is a structurally conserved and functionally essential component of the COMPASS family of histone methyltransferases responsible for H3K4 trimethylation. This minimalist helix-groove interface plays a critical allosteric role in stabilizing ASH2L, aligning the catalytic SET domain on nucleosomes, and enabling efficient methylation of chromatin targets. Recent structural, biochemical, and genetic studies have demonstrated that disrupting this contact-whether by point mutation, domain deletion, or competitive peptides-leads to widespread collapse of H3K4me3, transcriptional silencing of oncogenic programs, and suppression of cell proliferation, particularly in MLL-rearranged and MYC-driven cancers. In parallel, chemical-biology tools and fragment-based screening efforts have begun to yield the first ligandable scaffolds, setting the stage for drug discovery targeting this axis. This review synthesizes the current knowledge surrounding the ASH2L-DPY30 interface, covering its molecular architecture, catalytic importance, disease relevance, and therapeutic tractability. We also discuss resistance mechanisms, assay platforms, and the challenges and opportunities for translating this target into a first-in-class epigenetic therapy. - Source: PubMed
Publication date: 2026/03/21
Kamel Emadeldin MAllam Ahmed ARudayni Hassan AAlkhedhairi SalehAhmed Noha AAlkhayl Faris F AbaLamsabhi Al Mokhtar