Methylation of H4 lysines 5, 8 and 12 by yeast Set5 calibrates chromatin stress responses

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Methylation of histones is central to chromatin regulation, and thus previously unknown mechanisms regulating genome function can be revealed through the discovery of new histone methyl marks. Here we identify Set5 as the first histone H4 methyltransferase, which monomethylates the critical H4 lysine residues 5, 8 and 12 in budding yeast. Set5's enzymatic activity functions together with the global chromatin-modifying complexes COMPASS and NuA4 to regulate cell growth and stress responses.

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Figure 1: Identification of Set5 as an H4 methyltransferase.
Figure 2: Set5 monomethylates H4 in cells.
Figure 3: Set5 functions with COMPASS and NuA4 complexes to regulate cell growth and stress responses.


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The authors are grateful to A. Morrison for critical discussions regarding the work and to members of the Gozani and Chua labs for insights. The authors also acknowledge S. Dent (The University of Texas MD Anderson Cancer Center), S. Briggs (Purdue University) and M. Cyert (Stanford University) for yeast strains and reagents. This work was supported in part by grants from the US National Institutes of Health (NIH) to O.G. (R01 GM079641) and to B.A.G. (DP2OD007447) and by a National Science Foundation CAREER award (to B.A.G.). G.M. was funded by a postdoctoral fellowship from the Ministerio de Ciencia e Innovación (Spain), and E.M.G. acknowledges support from a Cancer Biology Program postdoctoral fellowship at Stanford University. N.L.Y. was supported with an NIH F32 National Research Service Award. O.G. is the recipient of an Ellison Senior Scholar in Aging Award.

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E.M.G., G.M. and O.G. conceived of and designed the experiments and wrote the manuscript. G.M. and E.M.G. contributed equally to the work and conducted all biochemical and cellular experiments. MS analysis was carried out by N.L.Y. and B.A.G.

Correspondence to Or Gozani.

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