Methylation of histone H3R2 by PRMT6 and H3K4 by an MLL complex are mutually exclusive
| Autor: | Bernhard Lüscher, Ernesto Guccione, Fabio Casadio, Henning Schuchlautz, Bruno Amati, Francesca Martinato, Matteo Cesaroni, Christian Bassi |
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| Rok vydání: | 2007 |
| Předmět: |
Chromatin Immunoprecipitation
Protein-Arginine N-Methyltransferases Biology Arginine Methylation Cell Line Epigenesis Genetic Histones Histone H3 Mice Epigenetics of physical exercise Histone arginine methylation Cell Line Tumor Histone methylation Histone code Animals Humans Promoter Regions Genetic Epigenomics Multidisciplinary Lysine Intracellular Signaling Peptides and Proteins Nuclear Proteins Histone-Lysine N-Methyltransferase Embryo Mammalian DNA-Binding Proteins Biochemistry Gene Expression Regulation Histone methyltransferase Multiprotein Complexes Transcription Factors |
| Zdroj: | Nature. 449(7164) |
| ISSN: | 1476-4687 |
| Popis: | Eukaryotic genomes are organized into active (euchromatic) and inactive (heterochromatic) chromatin domains. Post-translational modifications of histones (or 'marks') are key in defining these functional states, particularly in promoter regions. Mutual regulatory interactions between these marks--and the enzymes that catalyse them--contribute to the shaping of this epigenetic landscape, in a manner that remains to be fully elucidated. We previously observed that asymmetric di-methylation of histone H3 arginine 2 (H3R2me2a) counter-correlates with di- and tri- methylation of H3 lysine 4 (H3K4me2, H3K4me3) on human promoters. Here we show that the arginine methyltransferase PRMT6 catalyses H3R2 di-methylation in vitro and controls global levels of H3R2me2a in vivo. H3R2 methylation by PRMT6 was prevented by the presence of H3K4me3 on the H3 tail. Conversely, the H3R2me2a mark prevented methylation of H3K4 as well as binding to the H3 tail by an ASH2/WDR5/MLL-family methyltransferase complex. Chromatin immunoprecipitation showed that H3R2me2a was distributed within the body and at the 3' end of human genes, regardless of their transcriptional state, whereas it was selectively and locally depleted from active promoters, coincident with the presence of H3K4me3. Hence, the mutual antagonism between H3R2 and H3K4 methylation, together with the association of MLL-family complexes with the basal transcription machinery, may contribute to the localized patterns of H3K4 tri-methylation characteristic of transcriptionally poised or active promoters in mammalian genomes. |
| Databáze: | OpenAIRE |
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