ArticlePLoS genetics2014
Histone methyltransferase MMSET/NSD2 alters EZH2 binding and reprograms the myeloma epigenome through global and focal changes in H3K36 and H3K27 methylation.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 159 papers, 1 of them a synthesis that pooled it.
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Who cites it
159 citing papers in PubMed, 1 synthesis or guideline pooled it, 236 citations in OpenAlex.
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- Expression profile of CASSIOPEIA patients refines prognostic value of MRD negativity in multiple myeloma.Blood cancer journal · 2026Observational
- Identification and Prognostic Analysis of Immune-Related Genes Co-Regulated by Key Histone Modifications in Breast Cancer.Current issues in molecular biology · 2026Article
- Deciphering epigenetic crosstalk in multiple myeloma pathogenesis and treatment.Clinical epigenetics · 2026Review
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- Selective Glucocorticoid Receptor Modulators of Immune Checkpoint Function.bioRxiv : the preprint server for biology · 2026Article
- Epigenetic reprogramming in multiple myeloma-Challenges and opportunities.International journal of cancer · 2026Review
- NSD2 upregulation is driven by high-risk HPV E6/E7 and disrupts epithelial differentiation in HPV-associated head and neck cancer.Journal of experimental & clinical cancer research : CR · 2026Article
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- The role of epigenetic modifications in hematological cancers.Frontiers in oncology · 2026Review
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- Navigating the evolving management of smoldering multiple myeloma.HemaSphere · 2026Review
- RVd and CyBorD therapies remodel B-cell maturation signaling and alter immune and clonal architecture in multiple myeloma.Cancer biology & therapy · 2025Article
- Mechanistic Insights and Advances of Bispecific T Cell Engaging Antibodies Therapy in Multiple Myeloma.Medicina (Kaunas, Lithuania) · 2025Review
- NSD Family-Mediated H3K36 Methylation in Human Cancer: Mechanisms and Therapeutic Opportunities.Biomedicines · 2025Review
- Identification of potential methyltransferase NSD2 enzymatic inhibitors through a multi-step structure-based drug design.Molecular diversity · 2025Article
- Article
- Aere perennius: how chromatin fidelity is maintained and lost in disease.NAR molecular medicine · 2025Review
- Post-Translational Modifications in Multiple Myeloma: Mechanisms of Drug Resistance and Therapeutic Opportunities.Biomolecules · 2025Review
99 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 4 institutions in 2 countries.
Funding
Abstract
Overexpression of the histone methyltransferase MMSET in t(4;14)+ multiple myeloma patients is believed to be the driving factor in the pathogenesis of this subtype of myeloma. MMSET catalyzes dimethylation of lysine 36 on histone H3 (H3K36me2), and its overexpression causes a global increase in H3K36me2, redistributing this mark in a broad, elevated level across the genome. Here, we demonstrate that an increased level of MMSET also induces a global reduction of lysine 27 trimethylation on histone H3 (H3K27me3). Despite the net decrease in H3K27 methylation, specific genomic loci exhibit enhanced recruitment of the EZH2 histone methyltransferase and become hypermethylated on this residue. These effects likely contribute to the myeloma phenotype since MMSET-overexpressing cells displayed increased sensitivity to EZH2 inhibition. Furthermore, we demonstrate that such MMSET-mediated epigenetic changes require a number of functional domains within the protein, including PHD domains that mediate MMSET recruitment to chromatin. In vivo, targeting of MMSET by an inducible shRNA reversed histone methylation changes and led to regression of established tumors in athymic mice. Together, our work elucidates previously unrecognized interplay between MMSET and EZH2 in myeloma oncogenesis and identifies domains to be considered when designing inhibitors of MMSET function.
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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.