Multivalent interactions by the set8 histone methyltransferase with its nucleosome substrate

Taverekere S. Girish, Robert K. McGinty, Song Tan

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Set8 is the only mammalian monomethyltransferase responsible for H4K20me1, a methyl mark critical for genomic integrity of eukaryotic cells. We present here a structural model for how Set8 uses multivalent interactions to bind and methylate the nucleosome based on crystallographic and solution studies of the Set8/nucleosome complex. Our studies indicate that Set8 employs its i-SET and c-SET domains to engage nucleosomal DNA 1 to 1.5 turns from the nucleosomal dyad and in doing so, it positions the SET domain for catalysis with H4 Lys20. Surprisingly, we find that a basic N-terminal extension to the SET domain plays an even more prominent role in nucleosome binding, possibly by making an arginine anchor interaction with the nucleosome H2A/H2B acidic patch. We further show that proliferating cell nuclear antigen and the nucleosome compete for binding to Set8 through this basic extension, suggesting a mechanism for how nucleosome binding protects Set8 from proliferating cell nuclear antigen-dependent degradation during the cell cycle.

Original languageEnglish (US)
Pages (from-to)1531-1543
Number of pages13
JournalJournal of Molecular Biology
Volume428
Issue number8
DOIs
StatePublished - Apr 24 2016

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Nucleosomes
Proliferating Cell Nuclear Antigen
Structural Models
Eukaryotic Cells
Catalysis
Arginine
histone methyltransferase
Cell Cycle
DNA

All Science Journal Classification (ASJC) codes

  • Molecular Biology

Cite this

Girish, Taverekere S. ; McGinty, Robert K. ; Tan, Song. / Multivalent interactions by the set8 histone methyltransferase with its nucleosome substrate. In: Journal of Molecular Biology. 2016 ; Vol. 428, No. 8. pp. 1531-1543.
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Multivalent interactions by the set8 histone methyltransferase with its nucleosome substrate. / Girish, Taverekere S.; McGinty, Robert K.; Tan, Song.

In: Journal of Molecular Biology, Vol. 428, No. 8, 24.04.2016, p. 1531-1543.

Research output: Contribution to journalArticle

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