ArticleProceedings of the National Academy of Sciences of the United States of America2009
MLL5, a trithorax homolog, indirectly regulates H3K4 methylation, represses cyclin A2 expression, and promotes myogenic differentiation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 1 of them a synthesis that pooled it.
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Who cites it
85 citing papers in PubMed, 1 synthesis or guideline pooled it, 126 citations in OpenAlex.
- Allele-specific control of rodent and human lncRNA KMT2E-AS1 promotes hypoxic endothelial pathology in pulmonary hypertension.Science translational medicine · 2024Pooled it
- Epigenetics in development, disease, and therapy: from mechanisms to clinical interventions.Science China. Life sciences · 2026Review
- The Functions and Regulatory Mechanisms of Histone Modifications in Skeletal Muscle Development and Disease.International journal of molecular sciences · 2025Review
- Comprehensive genome annotation of the model ciliate Tetrahymena thermophila by in-depth epigenetic and transcriptomic profiling.Nucleic acids research · 2025Article
- Epigenetic control of skeletal muscle atrophy.Cellular & molecular biology letters · 2024Review
- A HIF-2α-dependentAnnals of translational medicine · 2024Article
- CanPharmaceuticals (Basel, Switzerland) · 2024Review
- Defining Biological and Biochemical Functions of Noncanonical SET Domain Proteins.Journal of molecular biology · 2024Review
- Isolation, identification, and induced differentiation of satellite cells from skeletal muscle of adult tree shrews.In vitro cellular & developmental biology. Animal · 2024Article
- Enhanced secretion of promyogenic exosomes by quiescent muscle cells.Frontiers in cell and developmental biology · 2024Article
- NMR-based comparative metabolomics of quiescent muscle cells.Journal of biosciences · 2024Article
- Lysine methylation signaling in skeletal muscle biology: from myogenesis to clinical insights.The Biochemical journal · 2023Review
- Epigenetic genes and epilepsy - emerging mechanisms and clinical applications.Nature reviews. Neurology · 2022Review
- MLL5 is involved in retinal photoreceptor maturation through facilitating CRX-mediated photoreceptor gene transactivation.iScience · 2022Article
- Reprogramming of the epigenome in neurodevelopmental disorders.Critical reviews in biochemistry and molecular biology · 2022Review
- mRNP granule proteins Fmrp and Dcp1a differentially regulate mRNP complexes to contribute to control of muscle stem cell quiescence and activation.Skeletal muscle · 2021Article
- MLL5 improves ATRA driven differentiation and promotes xenotransplant engraftment in acute promyelocytic leukemia model.Cell death & disease · 2021Article
- Epigenetic regulation of satellite cell fate during skeletal muscle regeneration.Skeletal muscle · 2021Review
- A crucial RNA-binding lysine residue in the Nab3 RRM domain undergoes SET1 and SET3-responsive methylation.Nucleic acids research · 2020Article
- MLL5α activates AR/NDRG1 signaling to suppress prostate cancer progression.American journal of cancer research · 2020Article
25 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Most cells in adult tissues are nondividing. In skeletal muscle, differentiated myofibers have exited the cell cycle permanently, whereas satellite stem cells withdraw transiently, returning to active proliferation to repair damaged myofibers. We have examined the epigenetic mechanisms operating in conditional quiescence by analyzing the function of a predicted chromatin regulator mixed lineage leukemia 5 (MLL5) in a culture model of reversible arrest. MLL5 is induced in quiescent myoblasts and regulates both the cell cycle and differentiation via a hierarchy of chromatin and transcriptional regulators. Knocking down MLL5 delays entry of quiescent myoblasts into S phase, but hastens S-phase completion. Cyclin A2 (CycA) mRNA is no longer restricted to S phase, but is induced throughout G(0)/G(1), with activation of the cell cycle regulated element (CCRE) in the CycA promoter. Overexpressed MLL5 physically associates with the CCRE and impairs its activity. MLL5 also regulates CycA indirectly: Cux, an activator of CycA promoter and S phase is induced in RNAi cells, and Brm/Brg1, CCRE-binding repressors that promote differentiation are repressed. In knockdown cells, H3K4 methylation at the CCRE is reduced, reflecting quantitative global changes in methylation. MLL5 appears to lack intrinsic histone methyl transferase activity, but regulates expression of histone-modifying enzymes LSD1 and SET7/9, suggesting an indirect mechanism. Finally, expression of muscle regulators Pax7, Myf5, and myogenin is impaired in MLL5 knockdown cells, which are profoundly differentiation defective. Collectively, our results suggest that MLL5 plays an integral role in novel chromatin regulatory mechanisms that suppress inappropriate expression of S-phase-promoting genes and maintain expression of determination genes in quiescent cells.
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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.