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The trithorax-group protein Lid is a histone H3 trimethyl-Lys4 demethylase

Abstract

Recent studies have demonstrated that histone methylation can be dynamically regulated through active demethylation. However, no demethylase specific to histone H3 trimethyl-Lys4 (H3K4me3) has been identified. Here we report that the Drosophila melanogaster protein 'little imaginal discs' (Lid), a JmjC domain–containing trithorax group protein, can demethylate H3K4me3. Consistent with its genetic classification, Lid positively regulates Hox gene expression in S2 cells.

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Figure 1: Lid is a histone demethylase with specificity for H3K4me3.
Figure 2: Multiple domains contribute to Lid enzymatic activity.
Figure 3: Lid localizes to interbands but does not colocalize with active RNA polymerase II.

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References

  1. Martin, C. & Zhang, Y. Nat. Rev. Mol. Cell Biol. 6, 838–849 (2005).

    Article  CAS  Google Scholar 

  2. Shi, Y. et al. Cell 119, 941–953 (2004).

    Article  CAS  Google Scholar 

  3. Klose, R.J., Kallin, E.M. & Zhang, Y. Nat. Rev. Genet. 7, 715–727 (2006).

    Article  CAS  Google Scholar 

  4. Tsukada, Y. et al. Nature 439, 811–816 (2006).

    Article  CAS  Google Scholar 

  5. Cloos, P.A. et al. Nature 442, 307–311 (2006).

    Article  CAS  Google Scholar 

  6. Fodor, B.D. et al. Genes Dev. 20, 1557–1562 (2006).

    Article  CAS  Google Scholar 

  7. Klose, R.J. et al. Nature 442, 312–316 (2006).

    Article  CAS  Google Scholar 

  8. Whetstine, J.R. et al. Cell 125, 467–481 (2006).

    Article  CAS  Google Scholar 

  9. Yamane, K. et al. Cell 125, 483–495 (2006).

    Article  CAS  Google Scholar 

  10. Benevolenskaya, E.V., Murray, H.L., Branton, P., Young, R.A. & Kaelin, W.G., Jr. Mol. Cell 18, 623–635 (2005).

    Article  CAS  Google Scholar 

  11. Lu, P.J. et al. J. Biol. Chem. 274, 15633–15645 (1999).

    Article  CAS  Google Scholar 

  12. Gildea, J.J., Lopez, R. & Shearn, A. Genetics 156, 645–663 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Xiao, B. et al. Nature 421, 652–656 (2003).

    Article  CAS  Google Scholar 

  14. Srinivasan, S. et al. Development 132, 1623–1635 (2005).

    Article  CAS  Google Scholar 

  15. Ng, H.H., Robert, F., Young, R.A. & Struhl, K. Mol. Cell 11, 709–719 (2003).

    Article  CAS  Google Scholar 

  16. Santos-Rosa, H. et al. Nature 419, 407–411 (2002).

    Article  CAS  Google Scholar 

  17. Beisel, C., Imhof, A., Greene, J., Kremmer, E. & Sauer, F. Nature 419, 857–862 (2002).

    Article  CAS  Google Scholar 

  18. Sedkov, Y. et al. Nature 426, 78–83 (2003).

    Article  CAS  Google Scholar 

  19. Henry, K.W. et al. Genes Dev. 17, 2648–2663 (2003).

    Article  CAS  Google Scholar 

  20. Kao, C.F. et al. Genes Dev. 18, 184–195 (2004).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank L. Fabrizio for help with mass spectrometry and S. Rogers and G. Rogers (University of North Carolina, Chapel Hill) for sharing fly reagents. This work was supported by US National Institutes of Health grants GM68804 (to Y.Z.), GM46567 (to R.S.J.) and P30 CA08748 (to P.T.). Y.Z. is an Investigator of the Howard Hughes Medical Institute. R.J.K. is funded by the Canadian Institutes of Heath Research.

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Authors and Affiliations

Authors

Contributions

N.L. and Y.Z. designed the experiments. N.L., J.Z., R.J.K., H.E.-B. and P.T. performed the experiments. Y.Z., N.L. and R.S.J. wrote the paper.

Corresponding author

Correspondence to Yi Zhang.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

JARID family of JmjC proteins. (PDF 243 kb)

Supplementary Fig. 2

Overexpression of Lid in S2 cells. (PDF 357 kb)

Supplementary Fig. 3

HDM activity of Lid mutant enzymes. (PDF 116 kb)

Supplementary Fig. 4

Lid distribution on polytene chromosomes. (PDF 95 kb)

Supplementary Methods (PDF 81 kb)

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Lee, N., Zhang, J., Klose, R. et al. The trithorax-group protein Lid is a histone H3 trimethyl-Lys4 demethylase. Nat Struct Mol Biol 14, 341–343 (2007). https://doi.org/10.1038/nsmb1216

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