A novel route to product specificity in the Suv4-20 family of histone H4K20 methyltransferases

DOI: 10.1093/nar/gkt776
PMID: 24049080

Authors: Stacey Southall (Institute of Cancer Research) , Nora Cronin (Institute of Structural and Molecular Biology) , Jon R. Wilson (Section of Structural Biology, The Institute of Cancer Research)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nucleic Acids Research

State: Published (Approved)
Published: September 2013

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.

Journal Keywords: Animals; Catalytic; Drosophila; Histone-Lysine; Histones; Mice; Models; Molecular; S-Adenosylmethionine; Substrate Specificity

Subject Areas: Biology and Bio-materials


Instruments: I02-Macromolecular Crystallography , I04-1-Macromolecular Crystallography (fixed wavelength)

Added On: 24/09/2013 09:54

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