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.

  • Article
  • Published:

Functional interaction between PML and SATB1 regulates chromatin-loop architecture and transcription of the MHC class I locus

Nature Cell Biology volume 9, pages 45–56 (2007)Cite this article

Abstract

The function of the subnuclear structure the promyelocytic leukaemia (PML) body is unclear largely because of the functional heterogeneity of its constituents. Here, we provide the evidence for a direct link between PML, higher-order chromatin organization and gene regulation. We show that PML physically and functionally interacts with the matrix attachment region (MAR)-binding protein, special AT-rich sequence binding protein 1 (SATB1) to organize the major histocompatibility complex (MHC) class I locus into distinct higher-order chromatin-loop structures. Interferon γ (IFNγ) treatment and silencing of either SATB1 or PML dynamically alter chromatin architecture, thus affecting the expression profile of a subset of MHC class I genes. Our studies identify PML and SATB1 as a regulatory complex that governs transcription by orchestrating dynamic chromatin-loop architecture.

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: SATB1 and PML interact in vivo and in vitro.
Figure 2: SATB1, PML and MARs form a functional complex.
Figure 3: The MHC class I locus is organized into distinct chromatin loops.
Figure 4: SATB1 and PML directly associate with specific genomic regions of MHC class I locus in vivo.
Figure 5: Involvement of SATB1 and PML in the chromatin-loop organization of the MHC class I locus before and after IFNγ treatment.
Figure 6: Interaction between SATB1 and PML is required for the distinct chromatin architecture of the MHC class I locus.
Figure 7: Compositional balance between SATB1 and individual PML isoforms determines the distinct chromatin architecture of the MHC class I locus.
Figure 8: SATB1–PML-mediated chromatin-loop architecture regulates transcription of specific MHC- I genes.

Similar content being viewed by others

References

  1. Spector, D. L. The dynamics of chromosome organization and gene regulation. Annu. Rev. Biochem. 72, 573–608 (2003).

    Article  CAS  PubMed  Google Scholar 

  2. Cai, S., Han, H. J. & Kohwi-Shigematsu, T. Tissue-specific nuclear architecture and gene expression regulated by SATB1. Nature Genet. 34, 42–51 (2003).

    Article  CAS  PubMed  Google Scholar 

  3. Yasui, D., Miyano, M., Cai, S., Varga-Weisz, P. & Kohwi-Shigematsu, T. SATB1 targets chromatin remodelling to regulate genes over long distances. Nature 419, 641–645 (2002).

    Article  CAS  PubMed  Google Scholar 

  4. Kumar, P. P., Purbey, P. K., Ravi, D. S., Mitra, D. & Galande S. Displacement of SATB1-bound histone deacetylase 1 corepressor by the human immunodeficiency virus type 1 transactivator induces expression of interleukin-2 and its receptor in T cells. Mol. Cell Biol. 25, 1620–1633 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  5. Galande, S., Dickinson, L. A., Mian, I. S., Sikorska, M. & Kohwi-Shigematsu, T. SATB1 cleavage by caspase 6 disrupts PDZ domain-mediated dimerization, causing detachment from chromatin early in T-cell apoptosis. Mol. Cell Biol. 21, 5591–5604 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Dickinson, L. A., Dickinson, C. D. & Kohwi-Shigematsu, T. An atypical homeodomain in SATB1 promotes specific recognition of the key structural element in a matrix attachment region. J. Biol. Chem. 272, 11463–11470 (1997).

    Article  CAS  PubMed  Google Scholar 

  7. Jensen, K., Shiels, C. & Freemont, P. S. PML protein isoforms and the RBCC/TRIM motif. Oncogene 20, 7223–7233 (2001).

    Article  CAS  PubMed  Google Scholar 

  8. Seeler, J. S. & Dejean, A. Nuclear and unclear functions of SUMO. Nature Rev. Mol. Cell Biol. 4, 690–699 (2003).

    Article  CAS  Google Scholar 

  9. Zhong, S. et al. Role of SUMO-1-modified PML in nuclear body formation. Blood 95, 2748–2752 (2000).

    CAS  PubMed  Google Scholar 

  10. Shiels, C. et al. PML bodies associate specifically with the MHC gene cluster in interphase nuclei. J. Cell Sci. 114, 3705–3716 (2001).

    CAS  PubMed  Google Scholar 

  11. Zhong, S., Salomoni, P. & Pandolfi, P. P. The transcriptional role of PML and the nuclear body. Nature Cell Biol. 2, E85–E90 (2000).

    Article  CAS  PubMed  Google Scholar 

  12. Wang, J. et al. Promyelocytic leukemia nuclear bodies associate with transcriptionally active genomic regions. J. Cell Biol. 164, 515–526 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Negorev, D. & Maul, G. G. Cellular proteins localized at and interacting within ND10/PML nuclear bodies/PODs suggest functions of a nuclear depot. Oncogene 20, 7234–7242 (2001).

    Article  CAS  PubMed  Google Scholar 

  14. Dekker, J., Rippe, K., Dekker, M. & Kleckner N. Capturing chromosome conformation. Science 295, 1306–1311 (2002).

    Article  CAS  PubMed  Google Scholar 

  15. Splinter, E., Grosveld, F. & de Laat, W. 3C technology: analyzing the spatial organization of genomic loci in vivo. Methods Enzymol. 375, 493–507 (2004).

    Article  CAS  PubMed  Google Scholar 

  16. Kohwi-Shigematsu, T., Maass, K. & Bode, J. A thymocyte factor SATB1 suppresses transcription of stably integrated matrix-attachment region-linked reporter genes. Biochemistry 6, 12005–12010 (1997).

    Article  Google Scholar 

  17. Zheng, P. et al. Proto-oncogene PML controls genes devoted to MHC class I antigen presentation. Nature 396, 373–376 (1998).

    Article  CAS  PubMed  Google Scholar 

  18. Singh, G. B., Kramer, J. A. & Krawetz, S. A. Mathematical model to predict regions of chromatin attachment to the nuclear matrix. Nucleic Acids Res. 25, 1419–1425 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Lavau, C. et al. The acute promyelocytic leukaemia-associated PML gene is induced by interferon. Oncogene 11, 871–876 (1995).

    CAS  PubMed  Google Scholar 

  20. Boehm, U., Klamp, T., Groot, M. & Howard, J. C. Cellular responses to interferon-γ. Annu. Rev. Immunol. 15, 749–795 (1997).

    Article  CAS  PubMed  Google Scholar 

  21. Horike, S., Cai, S., Miyano, M., Cheng, J. F. & Kohwi-Shigematsu, T. Loss of silent-chromatin looping and impaired imprinting of DLX5 in Rett syndrome. Nature Genet. 37, 31–40 (2005).

    Article  CAS  PubMed  Google Scholar 

  22. Kiesslich, A., von Mikecz, A. & Hemmerich, P. Cell cycle-dependent association of PML bodies with sites of active transcription in nuclei of mammalian cells. J. Struct. Biol. 140, 167–179 (2002).

    Article  CAS  PubMed  Google Scholar 

  23. Platani, M. & Lamond, A. I. Nuclear organisation and subnuclear bodies. Prog. Mol. Subcell. Biol. 35, 1–22 (2004).

    PubMed  Google Scholar 

  24. Bischof, O., Nacerddine, K. & Dejean, A. Human papillomavirus oncoprotein E7 targets the promyelocytic leukemia protein and circumvents cellular senescence via the Rb and p53 tumor suppressor pathways. Mol. Cell Biol. 25, 1013–1024 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Fogal, V. et al. Regulation of p53 activity in nuclear bodies by a specific PML isoform. EMBO J. 19, 6185–6195 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Wiesmeijer, K., Molenaar, C., Bekeer, I. M., Tanke, H. J. & Dirks, R. W. Mobile foci of Sp100 do not contain PML: PML bodies are immobile but PML and Sp100 proteins are not. J Struct. Biol. 140, 180–188 (2002).

    Article  CAS  PubMed  Google Scholar 

  27. Bloch, D. B. et al. Structural and functional heterogeneity of nuclear bodies. Mol. Cell Biol. 19, 4423–4430 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Chang, K. S., Fan, Y. H., Andreeff, M., Liu, J. & Mu, Z. M. The PML gene encodes a phosphoprotein associated with the nuclear matrix. Blood 85, 3646–3653 (1995).

    CAS  PubMed  Google Scholar 

  29. Bulger, M. & Groudine, M. Looping versus linking: toward a model for long-distance gene activation. Genes Dev. 13, 2465–2477 (1999).

    Article  CAS  PubMed  Google Scholar 

  30. Carter, D., Chakalova, L., Osborne, C. S., Dai, Y. F. & Fraser, P. Long-range chromatin regulatory interactions in vivo. Nature Genet. 32, 623–626 (2002).

    Article  CAS  PubMed  Google Scholar 

  31. Spilianakis, C. G. & Flavell, R. A. Long-range intrachromosomal interactions in the T helper type 2 cytokine locus. Nature Immunol. 5, 1017–1027 (2004).

    Article  CAS  Google Scholar 

  32. Murrell, A., Heeson, S. & Reik, W. Interaction between differentially methylated regions partitions the imprinted genes Igf2 and H19 into parent-specific chromatin loops. Nature Genet. 36, 889–893 (2004).

    Article  CAS  PubMed  Google Scholar 

  33. Volpi, E. V. et al. Large-scale chromatin organization of the major histocompatibility complex and other regions of human chromosome 6 and its response to interferon in interphase nuclei. J. Cell Sci. 113, 1565–1576 (2000).

    CAS  PubMed  Google Scholar 

  34. Hawkins, S. M., Kohwi-Shigematsu, T. & Skalnik, D. G. The matrix attachment region-binding protein SATB1 interacts with multiple elements within the gp91phox promoter and is down-regulated during myeloid differentiation. J. Biol. Chem. 276, 44472–44480 (2001).

    Article  CAS  PubMed  Google Scholar 

  35. Kumar P. P. et al. Phosphorylation of SATB1, a global gene regulator, acts as a molecular switch regulating its transcriptional activity in vivo. Mol Cell. 22, 231–243 (2006).

    Article  Google Scholar 

  36. Bruno, S. et al. The PML gene is not involved in the regulation of MHC class I expression in human cell lines. Blood 101, 3514–3519 (2003).

    Article  CAS  PubMed  Google Scholar 

  37. Larghero, J. et al. Alteration of the PML proto-oncogene in leukemic cells does not abrogate expression of MHC class I antigens. Leukemia 13, 1295–1296 (1999).

    Article  CAS  PubMed  Google Scholar 

  38. Kumanovics, A., Takada, T. & Lindahl, K. F. Genomic organization of the mammalian MHC. Annu. Rev. Immunol. 21, 629–657 (2003).

    Article  CAS  PubMed  Google Scholar 

  39. de Laat, W. & Grosveld, F. Spatial organization of gene expression: the active chromatin hub. Chromosome Res. 11, 447–459 (2003).

    Article  CAS  PubMed  Google Scholar 

  40. Kohwi-Shigematsu, T., de Belle, I., Dickinson, L. A., Galande, S. & Kohwi, Y. Identification of base-unpairing region (BUR)-binding proteins and characterization of their in vivo binding sequences. Methods Cell Biol. 53, 323–354 (1998).

    Article  CAS  PubMed  Google Scholar 

  41. Seo, J., Lozano, M. M. & Dudley, J. P. Nuclear matrix binding regulates SATB1-mediated transcriptional repression. J. Biol. Chem. 280, 24600–24609 (2005).

    Article  CAS  PubMed  Google Scholar 

  42. Dickinson, L. A., Joh, T., Kohwi, Y. & Kohwi-Shigematsu, T. A tissue-specific MAR/SAR binding protein with unusual binding site recognition. Cell 70, 631–645 (1992).

    Article  CAS  PubMed  Google Scholar 

  43. Weis, K. et al. Retinoic acid regulates aberrant nuclear localization of PML-RAR α in acute promyelocytic leukemia cells. Cell 76, 345–356 (1994).

    Article  CAS  PubMed  Google Scholar 

  44. Grande, M. A. et al. PML-containing nuclear bodies: their spatial distribution in relation to other nuclear components. J. Cell Biochem. 63, 280–291 (1996).

    Article  CAS  PubMed  Google Scholar 

  45. Rampalli, S. et al. Stimulation of Tat-independent transcriptional processivity from the HIV-1 LTR promoter by matrix attachment regions. Nucleic Acids Res. 31, 3248–3256 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank C. Maki for PML amino-terminal deletion constructs, F. Mercurio for pcDNA–IKKα and T. Kohwi-Shigematsu for anti-SATB1. Work was supported by grants from the Department of Biotechnology, Government of India, the Wellcome Trust, UK, the Ligue Nationale Contre le Cancer, the Fondation de France, the European Economic Community 'Intact', and the Association Laurette Fugain. O.B. is a senior research fellow from the Centre National de la Recherche Scientifique. P.K., D.N. and P.K.P are supported by fellowships from the Council of Scientific and Industrial Research, India. S.G. is an international senior research fellow of the Wellcome Trust.

Author information

Author notes

  1. Pavan Kumar P. and Oliver Bischof: These authors contributed equally to this work.

Authors and Affiliations

  1. National Centre for Cell Science, Ganeshkhind, Pune, 411007, India

    Pavan Kumar P., Prabhat Kumar Purbey, Dimple Notani & Sanjeev Galande

  2. Unité d'Organisation Nucléaire et Oncogénèse/INSERM U579, Institut Pasteur, 28, rue du Docteur Roux, Paris, 75724, Cedex 15, France

    Pavan Kumar P., Oliver Bischof & Anne Dejean

  3. Max-Planck-Institute for Biophysical Chemistry, Bioanalytical Mass Spectrometry Group, Am Fassberg 11, Goettingen, D-37077, Germany

    Henning Urlaub

Authors
  1. Pavan Kumar P.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Oliver Bischof
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Prabhat Kumar Purbey
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dimple Notani
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Henning Urlaub
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Anne Dejean
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sanjeev Galande
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sanjeev Galande.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Information

Supplementary figures S1, S2, S3, S4, S5 and Supplementary Methods (PDF 944 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

P., P., Bischof, O., Purbey, P. et al. Functional interaction between PML and SATB1 regulates chromatin-loop architecture and transcription of the MHC class I locus. Nat Cell Biol 9, 45–56 (2007). https://doi.org/10.1038/ncb1516

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncb1516

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing