Protein arginine methyltransferases (PRMTs) catalyze the transfer of methyl groups to specific arginine residues of histones and nonhistone proteins. There are nine members in the PRMT family (PRMT1 to PRMT9), and PRMT1 is a dominant member catalyzing majority of arginine methylation in the cell. However, none of the PRMTs is active with recombinant nucleosome as substrate in vitro. Here, we report the discovery of the first in class novel crosstalk between histone H4 lysine 20 (H4K20) monomethylation on nucleosome by SETD8 and histone H4 arginine 3 (H4R3) methylation by PRMT1 in vitro. Full kinetic characterization and mass spectrometry analysis indicated that PRMT1 is only active with recombinant nucleosomes monomethylated at H4K20 by SETD8. These data suggests that the level of activity of PRMT1 could potentially be regulated selectively by SETD8 in various pathways, providing a new approach for discovery of selective regulators of PRMT1 activity.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bbagrm.2023.194922 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
SETD8 inhibition targets cancer cells with increased rates of ribosome biogenesis.
Cell Death Dis
September 2024
Genomic Instability Group, Spanish National Cancer Research Centre (CNIO), Madrid, 28029, Spain.
SETD8 is a methyltransferase that is overexpressed in several cancers, which monomethylates H4K20 as well as other non-histone targets such as PCNA or p53. We here report novel SETD8 inhibitors, which were discovered while trying to identify chemicals that prevent 53BP1 foci formation, an event mediated by H4K20 methylation. Consistent with previous reports, SETD8 inhibitors induce p53 expression, although they are equally toxic for p53 proficient or deficient cells.
View Article and Find Full Text PDFBeyond histones: the elusive substrates of chromatin regulators.
Genes Dev
June 2024
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm 10691, Sweden
Gene transcription is intimately linked to chromatin state and histone modifications. However, the enzymes mediating these post-translational modifications have many additional, nonhistone substrates, making it difficult to ascribe the most relevant modification. In this issue of , Crain and colleagues (doi:10.
View Article and Find Full Text PDFMono-methylated histones control PARP-1 in chromatin and transcription.
Elife
May 2024
Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, United States.
PARP-1 is central to transcriptional regulation under both normal and stress conditions, with the governing mechanisms yet to be fully understood. Our biochemical and ChIP-seq-based analyses showed that PARP-1 binds specifically to active histone marks, particularly H4K20me1. We found that H4K20me1 plays a critical role in facilitating PARP-1 binding and the regulation of PARP-1-dependent loci during both development and heat shock stress.
View Article and Find Full Text PDFTrophoblast PR-SET7 dysfunction induces viral mimicry response and necroptosis associated with recurrent miscarriage.
Proc Natl Acad Sci U S A
June 2023
Fujian Provincial Key Laboratory of Reproductive Health Research, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China.
Recurrent miscarriage (RM) is a distressing pregnancy complication. While the etiology of RM remains unclear, growing evidence has indicated the relevance of trophoblast impairment to the pathogenesis of RM. PR-SET7 is the sole enzyme catalyzing monomethylation of H4K20 (H4K20me1) and has been implicated in many pathophysiological processes.
View Article and Find Full Text PDFHistone H4K20 monomethylation enables recombinant nucleosome methylation by PRMT1 in vitro.
Biochim Biophys Acta Gene Regul Mech
June 2023
Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario M5S 1A8, Canada; Drug Discovery Program, Ontario Institute for Cancer Research, Toronto, Ontario, Canada; Structural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7, Canada. Electronic address:
Protein arginine methyltransferases (PRMTs) catalyze the transfer of methyl groups to specific arginine residues of histones and nonhistone proteins. There are nine members in the PRMT family (PRMT1 to PRMT9), and PRMT1 is a dominant member catalyzing majority of arginine methylation in the cell. However, none of the PRMTs is active with recombinant nucleosome as substrate in vitro.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!