Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

HDAC4 mediates transcriptional repression by the acute promyelocytic leukaemia-associated protein PLZF

Oncogene volume 23, pages 8777–8784 (2004)Cite this article

Abstract

PLZF, the promyelocytic leukaemia zinc-finger protein, is a transcriptional repressor essential to development. In some acute leukaemias, a chromosomal translocation fusing the PLZF gene to that encoding the retinoic acid receptor RARα gives rise to a fusion protein, PLZF–RARα, thought to be responsible for constitutive repression of differentiation-associated genes in these cells. Repression by both PLZF and PLZF–RARα is sensitive to the histone deacetylase inhibitor TSA, and PLZF was previously shown to interact physically with HDAC1, a class I histone deacetylase. We here asked whether class II histone deacetylases, known to be generally involved in differentiation processes, participate in the repression mediated by PLZF and PLZF–RARα, and found that PLZF interacts with HDAC4 in both GST-pull-down and co-immunoprecipitation assays. Furthermore, HDAC4 is indeed involved in PLZF and PLZF–RARα-mediated repression, since an enzymatically dead mutant of HDAC4 released the repression, as did an siRNA that blocks HDAC4 expression. Taken together, our data indicate that recruitment of HDAC4 is necessary for PLZF-mediated repression in both normal and leukaemic cells.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  • Ahmed N, Williams JF and Weidemann MJ . (1993). Biochem. Mol. Biol. Int., 29, 1055–1067.

  • Bardwell VJ and Treisman R . (1994). Genes Dev., 8, 1664–1677.

  • Barna M, Hawe N, Niswander L and Pandolfi PP . (2000). Nat. Genet., 25, 166–172.

  • Bereshchenko OR, Gu W and Dalla-Favera R . (2002). Nat. Genet., 32, 606–613.

  • Borghi S, Molinari S, Razzini G, Parise F, Battini R and Ferrari S . (2001). J. Cell Sci., 114, 4477–4483.

  • Chan JK, Sun L, Yang XJ, Zhu G and Wu Z . (2003). J. Biol. Chem., 278, 23515–23521.

  • Chen SJ, Zelent A, Tong JH, Yu HQ, Wang ZY, Derre J, Berger R, Waxman S and Chen Z . (1993). J. Clin. Invest., 91, 2260–2267.

  • David G, Alland L, Hong SH, Wong CW, Depinho RA and Dejean A . (1998). Oncogene, 16, 2549–2556.

  • Davis FJ, Gupta M, Camoretti-Mercado B, Schwartz RJ and Gupta MP . (2003). J. Biol. Chem., 278, 20047–20058.

  • de Ruijter AJ, van Gennip AH, Caron HN, Kemp S and van Kuilenburg AB . (2003). Biochem. J., 370, 737–749.

  • Dhordain P, Albagli O, Lin RJ, Ansieau S, Quief S, Leutz A, Kerckaert JP, Evans RM and Leprince D . (1997). Proc. Natl. Acad. Sci. USA, 94, 10762–10767.

  • Dressel U, Bailey PJ, Wang SC, Downes M, Evans RM and Muscat GE . (2001). J. Biol. Chem., 276, 17007–17013.

  • Durand B, Saunders M, Leroy P, Leid M and Chambon P . (1992). Cell, 71, 73–85.

  • Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K and Tuschl T . (2001). Nature, 411, 494–498.

  • Fischle W, Dequiedt F, Hendzel MJ, Guenther MG, Lazar MA, Voelter W and Verdin E . (2002). Mol. Cell, 9, 45–57.

  • Fischle W, Kiermer V, Dequiedt F and Verdin E . (2001). Biochem. Cell Biol., 79, 337–348.

  • Grignani F, Dematteis S, Nervi C, Tomassoni L, Gelmetti V, Cioce M, Fanelli M, Ruthardt M, Ferrara FF, Zamir I, Seiser C, Grignani F, Lazar MA, Minucci S and Pelicci PG . (1998). Nature, 391, 815–818.

  • Groisman R, Masutani H, Leibovitch MP, Robin P, Soudant I, Trouche D and Harel-Bellan A . (1996). J. Biol. Chem., 271, 5258–5264.

  • Guidez F, Ivins S, Zhu J, Soderstrom M, Waxman S and Zelent A . (1998). Blood, 91, 2634–2642.

  • Hassig CA, Fleischer TC, Billin AN, Schreiber SL and Ayer DE . (1997). Cell, 89, 341–347.

  • Hassig CA, Tong JK, Fleischer TC, Owa T, Grable PG, Ayer DE and Schreiber SL . (1998). Proc. Natl. Acad. Sci. USA, 95, 3519–3524.

  • Heinzel T, Lavinsky RM, Mullen TM, Soderstrom M, Laherty CD, Torchia J, Yang WM, Brard G, Ngo SD, Davie JR, Seto E, Eisenman RN, Rose DW, Glass CK and Rosenfeld MG . (1997). Nature, 387, 43–48.

  • Hoatlin ME, Zhi Y, Ball H, Silvey K, Melnick A, Stone S, Arai S, Hawe N, Owen G, Zelent A and Licht JD . (1999). Blood, 94, 3737–3747.

  • Hong SH, David G, Wong CW, Dejean A and Privalsky ML . (1997). Proc. Natl. Acad. Sci. USA, 94, 9028–9033.

  • Kao GD, McKenna WG, Guenther MG, Muschel RJ, Lazar MA and Yen TJ . (2003). J. Cell. Biol., 160, 1017–1027.

  • Kao HY, Verdel A, Tsai CC, Simon C, Juguilon H and Khochbin S . (2001). J. Biol. Chem., 276, 47496–47507.

  • Lemercier C, Brocard MP, Puvion-Dutilleul F, Kao HY, Albagli O and Khochbin S . (2002). J. Biol. Chem., 277, 22045–22052.

  • Licht JD, Shaknovich R, English MA, Melnick A, Li JY, Reddy JC, Dong S, Chen SJ, Zelent A and Waxman S . (1996). Oncogene, 12, 323–336.

  • Lin RJ, Nagy L, Inoue S, Shao W, Miller Jr WH and Evans RM . (1998). Nature, 391, 811–814.

  • Lu J, McKinsey TA, Zhang CL and Olson EN . (2000). Mol. Cells, 6, 233–244.

  • Magnaghi-Jaulin L, Groisman R, Naguibneva I, Robin P, Lorain S, Le Villain JP, Troalen F, Trouche D and Harel-Bellan A . (1998). Nature, 391, 601–605.

  • McConnell MJ, Chevallier N, Berkofsky-Fessler W, Giltnane JM, Malani RB, Staudt LM and Licht JD . (2003). Mol. Cell. Biol., 23, 9375–9388.

  • McKinsey TA, Zhang CL, Lu J and Olson EN . (2000). Nature, 408, 106–111.

  • Melnick A, Carlile G, Ahmad KF, Kiang CL, Corcoran C, Bardwell V, Prive GG and Licht JD . (2002). Mol. Cell. Biol., 22, 1804–1818.

  • Miska EA, Langley E, Wolf D, Karlsson C, Pines J and Kouzarides T . (2001). Nucleic Acids Res., 29, 3439–3447.

  • Nagy L, Kao HY, Chakravarti D, Lin RJ, Hassig CA, Ayer DE, Schreiber SL and Evans RM . (1997). Cell, 89, 373–380.

  • Nanba D, Mammoto A, Hashimoto K and Higashiyama S . (2003). J. Cell Biol., 163, 489–502.

  • Reid A, Gould A, Brand N, Cook M, Strutt P, Li J, Licht J, Waxman S, Krumlauf R and Zelent A . (1995). Blood, 86, 4544–4552.

  • Senbonmatsu T, Saito T, Landon EJ, Watanabe O, Price Jr E, Roberts RL, Imboden H, Fitzgerald TG, Gaffney FA and Inagami T . (2003). EMBO J., 22, 6471–6482.

  • Shaknovich R, Yeyati PL, Ivins S, Melnick A, Lempert C, Waxman S, Zelent A and Licht JD . (1998). Mol. Cell. Biol., 18, 5533–5545.

  • Taunton J, Hassig CA and Schreiber SL . (1996). Science, 272, 408–411.

  • Verdel A and Khochbin S . (1999). J. Biol. Chem., 274, 2440–2445.

  • Wang AH, Bertos NR, Vezmar M, Pelletier N, Crosato M, Heng HH, Th'ng J, Han J and Yang XJ . (1999). Mol. Cell. Biol., 19, 7816–7827.

  • Watamoto K, Towatari M, Ozawa Y, Miyata Y, Okamoto M, Abe A, Naoe T and Saito H . (2003). Oncogene, 22, 9176–9184.

  • Wolffe AP and Guschin D . (2000). J. Struct. Biol., 129, 102–122.

  • Wong CW and Privalsky ML . (1998). J. Biol. Chem., 273, 27695–27702.

  • Zelent A, Guidez F, Melnick A, Waxman S and Licht JD . (2001). Oncogene, 20, 7186–7203.

Download references

Acknowledgements

We thank XJ Wang for providing HDAC4 expression vectors, S Khochbin for HDAC5 and 6 expression vectors, W-M Yang for HDAC2 and 3 expression vectors, Z Wu for xp-HD4-(1–208) expression vector and P Chambon for RARE-TK-CAT and anti-RARα antibodies. This work was supported by grants from ARC and the European 5th FP (grant QLG1-1999-00866). MM was supported by the CNRS, RF by the Comité du Val d'Oise de la Ligue contre le Cancer.

Author information

Author notes

  1. Anne Chauchereau and Marion Mathieu: These two authors contributed equally to this work

Authors and Affiliations

  1. UPR 9079 CNRS-Ligue Nationale Contre le Cancer, Institut André Lwoff, 7 rue Guy Môquet, Villejuif, 94800, France

    Anne Chauchereau, Marion Mathieu, Julie de Saintignon, Roger Ferreira, Linda L Pritchard & Annick Harel-Bellan

  2. Laboratoire de Cytométrie, Institut André Lwoff, 7 rue Guy Môquet, Villejuif, 94800, France

    Zohair Mishal

  3. INSERM U579, Institut Pasteur, 28 rue du Dr Roux, Paris, 75015, France

    Anne Dejean

Authors
  1. Anne Chauchereau
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marion Mathieu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Julie de Saintignon
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Roger Ferreira
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Linda L Pritchard
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zohair Mishal
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Anne Dejean
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Annick Harel-Bellan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Annick Harel-Bellan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chauchereau, A., Mathieu, M., de Saintignon, J. et al. HDAC4 mediates transcriptional repression by the acute promyelocytic leukaemia-associated protein PLZF. Oncogene 23, 8777–8784 (2004). https://doi.org/10.1038/sj.onc.1208128

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1208128

Keywords

This article is cited by

Search

Advanced search

Quick links