Article ID Journal Published Year Pages File Type
5533080 Journal of Molecular Biology 2017 9 Pages PDF
Abstract

•Set3 PHD finger binds H3K4me3 and H3K4me2 with comparable affinities.•Composition of the methyllysine-binding pocket confers selectivity.•The Set3-like aromatic cage is not sufficient to induce binding of Set4 to H3.

The plant homeodomain (PHD) finger of Set3 binds methylated lysine 4 of histone H3 in vitro and in vivo; however, precise selectivity of this domain has not been fully characterized. Here, we explore the determinants of methyllysine recognition by the PHD fingers of Set3 and its orthologs. We use X-ray crystallographic and spectroscopic approaches to show that the Set3 PHD finger binds di- and trimethylated states of H3K4 with comparable affinities and employs similar molecular mechanisms to form complexes with either mark. Composition of the methyllysine-binding pocket plays an essential role in determining the selectivity of the PHD fingers. The finding that the histone-binding activity is not conserved in the PHD finger of Set4 suggests different functions for the Set3 and Set4 paralogs.

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Life Sciences Biochemistry, Genetics and Molecular Biology Cell Biology
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