A novel route to product specificity in the Suv4-20 family of histone H4K20 methyltransferases
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ICR Authors
Authors
Southall, SM
Cronin, NB
Wilson, JR
Cronin, NB
Wilson, JR
Document Type
Journal Article
Date
2014-01-01
Date Accepted
Abstract
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.
Citation
NUCLEIC ACIDS RESEARCH, 2014, 42 pp. 661 - 671
Source Title
Publisher
OXFORD UNIV PRESS
ISSN
0305-1048
eISSN
1362-4962
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Research Team
Chromatin Regulation