Demethylation of trimethylated histone H3 Lys4 in vivo by JARID1 JmjC proteins

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Abstract

Histone H3 Lys4 trimethylation (H3-K4me3) is a conserved mark of actively transcribed chromatin. Using a conditional mutant of the yeast H3-K4 methyltransferase, Set1p, we demonstrate rapid turnover of H3-K4me3 and H3-K4me2 in vivo and show this process requires Yjr119Cp, of the JARID1 family of JmjC proteins. Ectopic overexpression of mouse Jarid1B, a Yjr119Cp homolog, greatly diminished H3-K4me3 and H3-K4me2 in HeLa cells, suggesting these proteins function as K4 demethylases in vivo.

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Figure 1: Genetic screen identifying Yjr119Cp as a yeast H3-K4me3 demethylase in vivo.
Figure 2: Ectopic expression of WT mouse Jarid1B, but not the JmjC H499A mutant, causes loss of H3-K4me3 and H3-K4me2.

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Acknowledgements

We thank M. Cleary (University of Iowa), D. Turner (University of Michigan) and A. Varshavsky (California Institute of Technology) for reagents, D. Gottschling, N. Fong, K. Glover and B. Erickson for discussion and technical help, and the Cancer Center sequencing facility of the University of Colorado Health Sciences Center. This work was supported by US National Institutes of Health grants R01GM063873 and T32-GM08730 to D.L.B. and D.J.S. D.J.S. is a member of the Medical Scientist Training Program.

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Correspondence to David L Bentley.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Genetic interaction between SET1 and YJR119C. (PDF 511 kb)

Supplementary Fig. 2

Loss of H3-K4me2/me3 in Hep3b cells overexpressing Jarid1B. (PDF 1738 kb)

Supplementary Fig. 3

CTD Ser2 phosphorylation in HeLa cells overexpressing Jarid1B. (PDF 818 kb)

Supplementary Fig. 4

CTD Ser5 phosphorylation in HeLa cells overexpressing Jarid1B. (PDF 1128 kb)

Supplementary Methods (PDF 104 kb)

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Seward, D., Cubberley, G., Kim, S. et al. Demethylation of trimethylated histone H3 Lys4 in vivo by JARID1 JmjC proteins. Nat Struct Mol Biol 14, 240–242 (2007) doi:10.1038/nsmb1200

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