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

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_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Southall SM,Cronin NB,Wilson JR

doi

10.1093/nar/gkt776

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

661-71

issue

1

eissn

0305-1048

issn

1362-4962

pii

gkt776

journal_volume

42

pub_type

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