ArticlePloS one2010
An Ash2L/RbBP5 heterodimer stimulates the MLL1 methyltransferase activity through coordinated substrate interactions with the MLL1 SET domain.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 119 citations in OpenAlex.
- COMPASS subunit Bre2 regulates chromatin remodeler Arp9 to control Aspergillus flavus aflatoxin synthesis and virulence.Nature communications · 2026Article
- Loss-of-function in RBBP5 results in a syndromic neurodevelopmental disorder associated with microcephaly.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Article
- Novel KMT2B gene mutation in MUC4 positive low-grade fibromyxoid sarcoma.Diagnostic pathology · 2024Article
- The Core Complex of Yeast COMPASS and Human Mixed-Lineage Leukemia (MLL), Structure, Function, and Recognition of the Nucleosome.Sub-cellular biochemistry · 2024Review
- Transcriptome analysis of the binucleate ciliateMolecular biology of the cell · 2023Article
- Histone lysine methyltransferase-related neurodevelopmental disorders: current knowledge and saRNA future therapies.Frontiers in cell and developmental biology · 2023Review
- PHF20 is crucial for epigenetic control of starvation-induced autophagy through enhancer activation.Nucleic acids research · 2022Article
- The role of Trithorax family regulating osteogenic and Chondrogenic differentiation in mesenchymal stem cells.Cell proliferation · 2022Review
- Article
- Loss of SET1/COMPASS methyltransferase activity reduces lifespan and fertility inLife science alliance · 2022Article
- Recruitment of MLL1 complex is essential for SETBP1 to induce myeloid transformation.iScience · 2022Article
- Plant defense compound triggers mycotoxin synthesis by regulating H2B ub1 and H3K4 me2/3 deposition.The New phytologist · 2021Article
- The role of reciprocal fusions in MLL-r acute leukemia: studying the chromosomal translocation t(6;11).Oncogene · 2021Article
- Structure, Activity and Function of the MLL2 (KMT2B) Protein Lysine Methyltransferase.Life (Basel, Switzerland) · 2021Review
- Review
- CRISPR screens in physiologic medium reveal conditionally essential genes in human cells.Cell metabolism · 2021Article
- Mechanism for DPY30 and ASH2L intrinsically disordered regions to modulate the MLL/SET1 activity on chromatin.Nature communications · 2021Article
- SET1/MLL family of proteins: functions beyond histone methylation.Epigenetics · 2021Review
- Insights on the regulation of the MLL/SET1 family histone methyltransferases.Biochimica et biophysica acta. Gene regulatory mechanisms · 2020Review
- KMT2C/D COMPASS complex-associated diseases [KClinical epigenetics · 2020Review
12 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Histone H3 lysine 4 (K4) methylation is a prevalent mark associated with transcription activation and is mainly catalyzed by the MLL/SET1 family histone methyltransferases. A common feature of the mammalian MLL/SET1 complexes is the presence of three core components (RbBP5, Ash2L and WDR5) and a catalytic subunit containing a SET domain. Unlike most other histone lysine methyltransferases, all four proteins are required for efficient H3 K4 methylation. Despite extensive efforts, mechanisms for how three core components regulate MLL/SET1 methyltransferase activity remain elusive. Here we show that a heterodimer of Ash2L and RbBP5 has intrinsic histone methyltransferase activity. This activity requires the highly conserved SPRY domain of Ash2L and a short peptide of RbBP5. We demonstrate that both Ash2L and the MLL1 SET domain are capable of binding to S-adenosyl-L- [methyl-(3)H] methionine in the MLL1 core complex. Mutations in the MLL1 SET domain that fail to support overall H3 K4 methylation also compromise SAM binding by Ash2L. Taken together, our results show that the Ash2L/RbBP5 heterodimer plays a critical role in the overall catalysis of MLL1 mediated H3 K4 methylation. The results we describe here provide mechanistic insights for unique regulation of the MLL1 methyltransferase activity. It suggests that both Ash2L/RbBP5 and the MLL1 SET domain make direct contacts with the substrates and contribute to the formation of a joint catalytic center. Given the shared core configuration among all MLL/SET1 family HMTs, it will be interesting to test whether the mechanism we describe here can be generalized to other MLL/SET1 family members in the future.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.