A PHD finger of NURF couples histone H3 lysine 4 trimethylation with chromatin remodelling (original) (raw)

Nature volume 442, pages 86–90 (2006)Cite this article

Abstract

Lysine methylation of histones is recognized as an important component of an epigenetic indexing system demarcating transcriptionally active and inactive chromatin domains. Trimethylation of histone H3 lysine 4 (H3K4me3) marks transcription start sites of virtually all active genes1,2,3,4. Recently, we reported that the WD40-repeat protein WDR5 is important for global levels of H3K4me3 and control of HOX gene expression5. Here we show that a plant homeodomain (PHD) finger of nucleosome remodelling factor (NURF), an ISWI-containing ATP-dependent chromatin-remodelling complex, mediates a direct preferential association with H3K4me3 tails. Depletion of H3K4me3 causes partial release of the NURF subunit, BPTF (bromodomain and PHD finger transcription factor), from chromatin and defective recruitment of the associated ATPase, SNF2L (also known as ISWI and SMARCA1), to the HOXC8 promoter. Loss of BPTF in Xenopus embryos mimics WDR5 loss-of-function phenotypes, and compromises spatial control of Hox gene expression. These results strongly suggest that WDR5 and NURF function in a common biological pathway in vivo, and that NURF-mediated ATP-dependent chromatin remodelling is directly coupled to H3K4 trimethylation to maintain Hox gene expression patterns during development. We also identify a previously unknown function for the PHD finger as a highly specialized methyl-lysine-binding domain.

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References

  1. Santos-Rosa, H. et al. Active genes are tri-methylated at K4 of histone H3. Nature 419, 407–411 (2002)
    Article ADS CAS PubMed Google Scholar
  2. Schneider, R. et al. Histone H3 lysine 4 methylation patterns in higher eukaryotic genes. Nature Cell Biol. 6, 73–77 (2004)
    Article CAS PubMed Google Scholar
  3. Bernstein, B. E. et al. Genomic maps and comparative analysis of histone modifications in human and mouse. Cell 120, 169–181 (2005)
    Article CAS PubMed Google Scholar
  4. Pokholok, D. K. et al. Genome-wide map of nucleosome acetylation and methylation in yeast. Cell 122, 517–527 (2005)
    Article CAS PubMed Google Scholar
  5. Wysocka, J. et al. WDR5 associates with histone H3 methylated at K4 and is essential for H3 K4 methylation and vertebrate development. Cell 121, 859–872 (2005)
    Article CAS PubMed Google Scholar
  6. Pray-Grant, M. G., Daniel, J. A., Schieltz, D., Yates, J. R. & Grant, P. A. Chd1 chromodomain links histone H3 methylation with SAGA- and SLIK-dependent acetylation. Nature 433, 434–438 (2005)
    Article ADS CAS PubMed Google Scholar
  7. Sims, R. J. et al. Human but not yeast CHD1 binds directly and selectively to histone H3 methylated at lysine 4 via its tandem chromodomains. J. Biol. Chem. 280, 41789–41792 (2005)
    Article CAS PubMed Google Scholar
  8. Santos-Rosa, H. et al. Methylation of histone H3 K4 mediates association of the Isw1p ATPase with chromatin. Mol. Cell 12, 1325–1332 (2003)
    Article CAS PubMed Google Scholar
  9. Tsukiyama, T. & Wu, C. Purification and properties of an ATP-dependent nucleosome remodeling factor. Cell 83, 1011–1020 (1995)
    Article CAS PubMed Google Scholar
  10. Barak, O. et al. Isolation of human NURF: a regulator of Engrailed gene expression. EMBO J. 22, 6089–6100 (2003)
    Article CAS PubMed PubMed Central Google Scholar
  11. Tsukiyama, T., Becker, P. B. & Wu, C. ATP-dependent nucleosome disruption at a heat-shock promoter mediated by binding of GAGA transcription factor. Nature 367, 525–532 (1994)
    Article ADS CAS PubMed Google Scholar
  12. Mizuguchi, G., Tsukiyama, T., Wisniewski, J. & Wu, C. Role of nucleosome remodeling factor NURF in transcriptional activation of chromatin. Mol. Cell 1, 141–150 (1997)
    Article CAS PubMed Google Scholar
  13. Hamiche, A., Sandaltzopoulos, R., Gdula, D. A. & Wu, C. ATP-dependent histone octamer sliding mediated by the chromatin remodeling complex NURF. Cell 97, 833–842 (1999)
    Article CAS PubMed Google Scholar
  14. Mizuguchi, G., Vassilev, A., Tsukiyama, T., Nakatani, Y. & Wu, C. ATP-dependent nucleosome remodeling and histone hyperacetylation synergistically facilitate transcription of chromatin. J. Biol. Chem. 276, 14773–14783 (2001)
    Article CAS PubMed Google Scholar
  15. Xiao, H. et al. Dual functions of largest NURF subunit NURF301 in nucleosome sliding and transcription factor interactions. Mol. Cell 8, 531–543 (2001)
    Article CAS PubMed Google Scholar
  16. Badenhorst, P., Voas, M., Rebay, I. & Wu, C. Biological functions of the ISWI chromatin remodeling complex NURF. Genes Dev. 16, 3186–3198 (2002)
    Article CAS PubMed PubMed Central Google Scholar
  17. Badenhorst, P. et al. The Drosophila nucleosome remodeling factor NURF is required for Ecdysteroid signaling and metamorphosis. Genes Dev. 19, 2540–2545 (2005)
    Article CAS PubMed PubMed Central Google Scholar
  18. Li, H. et al. Molecular basis for site-specific read-out of histone H3K4me3 by the BPTF PHD finger of NURF. Nature advance online publication, doi:10.1038/nature04802 (21 May 2006).
  19. Méndez, J. & Stillman, B. Chromatin association of human origin recognition complex, cdc6, and minichromosome maintenance proteins during the cell cycle: assembly of prereplication complexes in late mitosis. Mol. Cell. Biol. 20, 8602–8612 (2000)
    Article PubMed PubMed Central Google Scholar
  20. Milne, T. A. et al. MLL targets SET domain methyltransferase activity to Hox gene promoters. Mol. Cell 10, 1107–1117 (2002)
    Article CAS PubMed Google Scholar
  21. Shi, X. et al. ING2 PHD domain links histone H3 lysine 4 methylation to active gene repression. Nature advance online publication, doi:10.1038/nature04835 (21 May 2006).
  22. Bienz, M. The PHD finger, a nuclear protein-interaction domain. Trends Biochem. Sci. 31, 35–40 (2006)
    Article CAS PubMed Google Scholar
  23. Dhalluin, C. et al. Structure and ligand of a histone acetyltransferase bromodomain. Nature 399, 491–496 (1999)
    Article ADS CAS PubMed Google Scholar
  24. Ragvin, A. et al. Nucleosome binding by the bromodomain and PHD finger of the transcriptional cofactor p300. J. Mol. Biol. 337, 773–788 (2004)
    Article CAS PubMed Google Scholar
  25. Zhou, Y. & Grummt, I. The PHD finger/bromodomain of NoRC interacts with acetylated histone H4K16 and is sufficient for rDNA silencing. Curr. Biol. 15, 1434–1438 (2005)
    Article CAS PubMed Google Scholar
  26. Dignam, J. D., Lebovitz, R. M. & Roeder, R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 11, 1475–1489 (1983)
    Article CAS PubMed PubMed Central Google Scholar
  27. Zegerman, P., Canas, B., Pappin, D. & Kouzarides, T. Histone H3 lysine 4 methylation disrupts binding of nucleosome remodeling and deacetylase (NuRD) repressor complex. J. Biol. Chem. 277, 11621–11624 (2002)
    Article CAS PubMed Google Scholar
  28. Nishioka, K. et al. Set9, a novel histone H3 methyltransferase that facilitates transcription by precluding histone tail modifications required for heterochromatin formation. Genes Dev. 16, 479–489 (2002)
    Article CAS PubMed PubMed Central Google Scholar

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Acknowledgements

We thank E. Bernstein, W. Herr and E. Duncan for critical reading of the manuscript, O. Gozani for communicating unpublished results, and D. Reinberg, W. Herr, R. Roeder and J. Tamkun for CHD1, WDR5, MLL and ISWI antibodies, respectively. T.S. thanks A. H. Brivanlou for support. J.W. is a D. Runyon CRF Fellow, T.A.M. is a Canadian Institutes of Health Research Fellow, and J.L is an ACS Postdoctoral Research Fellow. C.W., J.L. and H.X. are supported by the US National Cancer Institute Intramural Research Program, and S.Y.K. and P.B. are supported by the BBSRC. C.D.A. acknowledges a MERIT Award from the NIH.

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Authors and Affiliations

  1. Laboratory of Chromatin Biology,
    Joanna Wysocka, Thomas A. Milne, Monika Kauer & C. David Allis
  2. Laboratory of Molecular Vertebrate Embryology,
    Tomek Swigut
  3. Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, New York, 1230 York Avenue, New York, 10021, USA
    Alan J. Tackett & Brian T. Chait
  4. Laboratory of Molecular Cell Biology, National Cancer Institute, NIH, Bethesda, Maryland, 20814, USA
    Hua Xiao, Joe Landry & Carl Wu
  5. Institute of Biomedical Research, University of Birmingham, Edgbaston, B15 2TT, UK
    So Yeon Kwon & Paul Badenhorst

Authors

  1. Joanna Wysocka
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  2. Tomek Swigut
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  3. Hua Xiao
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  4. Thomas A. Milne
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  5. So Yeon Kwon
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  6. Joe Landry
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  7. Monika Kauer
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  8. Alan J. Tackett
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  9. Brian T. Chait
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  10. Paul Badenhorst
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  11. Carl Wu
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  12. C. David Allis
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Correspondence toCarl Wu or C. David Allis.

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Wysocka, J., Swigut, T., Xiao, H. et al. A PHD finger of NURF couples histone H3 lysine 4 trimethylation with chromatin remodelling.Nature 442, 86–90 (2006). https://doi.org/10.1038/nature04815

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Editorial Summary

Histones decoded

Four papers in this issue tackle the hot topic of chromatin remodelling, specifically, how methyl marks on chromatin are 'read' by the proteins that interact with them. Two report on BPTF (bromodomain and PHD domain transcription factor), a subunit of NURF, the nucleosome remodelling factor. It contains a domain known as a PHD finger, which is shown to bind to histone H3 trimethylated at lysine 4 (H3K4) and to maintain proper activity at developmentally critical HOX genes. The accompanying structural study of the complex explains how the site specificity for H3K4 is achieved. The two other papers reveal that the PHD domain of tumour suppressor ING2 also recognizes trimethylated H3K4, and link the histone mark to repression of transcription. The four papers together establish certain PHD finger domains as previously unrecognized chromatin-binding modules. In a News and Views piece, Peter B. Becker discusses what these papers tell us about the function of the chemical modifications of histone tails.

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