A novel route to product specificity in the Suv4-20 family of histone H4K20 methyltransferases
| Autor: | Jon R. Wilson, Stacey M. Southall, Nora Cronin |
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| Rok vydání: | 2013 |
| Předmět: |
Models
Molecular S-Adenosylmethionine Molecular Sequence Data EZH2 Histone-Lysine N-Methyltransferase Biology Substrate Specificity Cell biology Histones Histone H4 Mice Histone H1 Biochemistry Structural Biology Catalytic Domain Histone methyltransferase Histone H2A Histone methylation Genetics Animals Drosophila Proteins Histone code Amino Acid Sequence Histone octamer |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| Popis: | The delivery of site-specific post-translational modifications to histones generates an epigenetic regulatory network that directs fundamental DNA-mediated processes and governs key stages in development. Methylation of histone H4 lysine-20 has been implicated in DNA repair, transcriptional silencing, genomic stability and regulation of replication. We present the structure of the histone H4K20 methyltransferase Suv4-20h2 in complex with its histone H4 peptide substrate and S-adenosyl methionine cofactor. Analysis of the structure reveals that the Suv4-20h2 active site diverges from the canonical SET domain configuration and generates a high degree of both substrate and product specificity. Together with supporting biochemical data comparing Suv4-20h1 and Suv4-20h2, we demonstrate that the Suv4-20 family enzymes take a previously mono-methylated H4K20 substrate and generate an exclusively di-methylated product. We therefore predict that other enzymes are responsible for the tri-methylation of histone H4K20 that marks silenced heterochromatin. |
| Databáze: | OpenAIRE |
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