ArticleThe Journal of biological chemistry2015
Biochemical reconstitution and phylogenetic comparison of human SET1 family core complexes involved in histone methylation.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 1 of them a synthesis that pooled it.
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Who cites it
72 citing papers in PubMed, 1 synthesis or guideline pooled it.
- NSD1 gene evolves under episodic selection within primates and mutations of specific exons in humans cause Sotos syndrome.BMC genomics · 2022Pooled it
- Promiscuous RNA binding by WDR5 remodels the KMT2A (MLL1) histone methyltransferase complex to an inactive state.Molecular cell · 2026Article
- Nuclear class 3 PI3K co-activates fasting-specific chromatin remodelling.Nature cell biology · 2026Article
- Probing the Cancer Mutational Landscape of KMT2 Regulatory Subunits.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Comparative characterization of chromatin-targeting mechanisms across seven H3K4 methyltransferases in Arabidopsis.Plant communications · 2026Article
- Update of the Methyltransferase Gene Family: Classification, Evolution and Biological Functions.Human genomics · 2026Review
- Insights into WDR5: unveiling its functions, regulation, and impact on skeletal muscle.Epigenetics · 2025Review
- Machine learning-driven prediction of substrates for enzymes introducing or removing protein post-translational modifications.Communications chemistry · 2025Article
- Canonical and Non-Canonical Functions of Histone H3K4 Methylation Modifiers in Cancer.Cancer science · 2025Review
- Regulation of H3K4me3 breadth and MYC expression by the SETD1B catalytic domain in MLL-rearranged leukemia.Leukemia · 2025Article
- Loss of function of the zinc finger homeobox 4 gene, ZFHX4, underlies a neurodevelopmental disorder.American journal of human genetics · 2025Article
- Mechanism of KMT2D-mediated epigenetic modification in IL-1β-induced nucleus pulposus cell degeneration.Histology and histopathology · 2025Article
- Histone lysine methyltransferases and their specific methylation marks show significant changes in mouse testes from young to older ages.Biogerontology · 2025Article
- Histone Methyltransferase SETD1B Maintains Cancer Stem Cell Niche by Regulating the Crosstalk between CD24 and Surface Adhesion Molecules in Hepatocellular Carcinoma.International journal of biological sciences · 2025Article
- O-GlcNAc transferase congenital disorder of glycosylation (OGT-CDG): Potential mechanistic targets revealed by evaluating the OGT interactome.The Journal of biological chemistry · 2024Review
- Loss-of-function of the Zinc Finger Homeobox 4 (medRxiv : the preprint server for health sciences · 2024Article
- Set1/COMPASS regulates growth, pathogenicity, and patulin biosynthesis of Penicillium expansum via H3K4 methylation and the interaction with PeVelB.Journal of advanced research · 2024Article
- Role of Histone Modifications in Kidney Fibrosis.Medicina (Kaunas, Lithuania) · 2024Review
- Article
- KMT2 Family of H3K4 Methyltransferases: Enzymatic Activity-dependent and -independent Functions.Journal of molecular biology · 2024Review
12 more citing papers are in PubMed but not listed here.
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4 authors.
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Abstract
Mixed lineage leukemia protein-1 (MLL1) is a member of the SET1 family of histone H3 lysine 4 (H3K4) methyltransferases that are required for metazoan development. MLL1 is the best characterized human SET1 family member, which includes MLL1-4 and SETd1A/B. MLL1 assembles with WDR5, RBBP5, ASH2L, DPY-30 (WRAD) to form the MLL1 core complex, which is required for H3K4 dimethylation and transcriptional activation. Because all SET1 family proteins interact with WRAD in vivo, it is hypothesized they are regulated by similar mechanisms. However, recent evidence suggests differences among family members that may reflect unique regulatory inputs in the cell. Missing is an understanding of the intrinsic enzymatic activities of different SET1 family complexes under standard conditions. In this investigation, we reconstituted each human SET1 family core complex and compared subunit assembly and enzymatic activities. We found that in the absence of WRAD, all but one SET domain catalyzes at least weak H3K4 monomethylation. In the presence of WRAD, all SET1 family members showed stimulated monomethyltransferase activity but differed in their di- and trimethylation activities. We found that these differences are correlated with evolutionary lineage, suggesting these enzyme complexes have evolved to accomplish unique tasks within metazoan genomes. To understand the structural basis for these differences, we employed a "phylogenetic scanning mutagenesis" assay and identified a cluster of amino acid substitutions that confer a WRAD-dependent gain-of-function dimethylation activity on complexes assembled with the MLL3 or Drosophila trithorax proteins. These results form the basis for understanding how WRAD differentially regulates SET1 family complexes in vivo.
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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.