Skip to main content

Advertisement

Log in

Tetramerization of SATB1 is essential for regulating of gene expression

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Special AT-rich sequence-binding protein 1 (SATB1) functions as a ‘genome organizer’ in tumorigenesis. Our previous report showed that SATB1 forms a tetramer through its N-terminal ubiquitin like domain rather than the proposed PDZ domain. In the present study, we aim to illustrate whether this oligomerization is critical to its function as a global repressor of gene expression in vivo. Luciferase and GST pull-down assays demonstrated that disrupting SATB1’s tetramerization not only affects the activities of promoters but also influences the recruitment of interaction partners. Furthermore, we developed stable cell lines that overexpressed either the SATB1 tetramer or STAB1 dimer (KWN–AAA) and monitored global gene expression. Gene expression profiling revealed that over 1000 genes were significantly upregulated or downregulated upon the overexpression of SATB1 or the SATB1 (KWN–AAA) mutant. These data implied that SATB1 might regulate gene expression through its different oligomerization state. In conclusion, we inferred that the oligomerization of SATB1 is pivotal to its function of different biological processes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

References

  1. Mao LJ, Yang CH, Fan L, Gao P, Yang DR, Xue BX, Zheng JN, Shan YX (2016) SATB1 promotes prostate cancer metastasis by the regulation of epithelial-mesenchymal transition. Biomed Pharmacother 79:1–8. doi:10.1016/j.biopha.2016.01.038

    Article  CAS  PubMed  Google Scholar 

  2. Han HJ, Russo J, Kohwi Y, Kohwi-Shigematsu T (2008) SATB1 reprogrammes gene expression to promote breast tumour growth and metastasis. Nature 452:187–193. doi:10.1038/nature06781

    Article  CAS  PubMed  Google Scholar 

  3. Mir R, Pradhan SJ, Patil P, Mulherkar R, Galande S (2016) Wnt/beta-catenin signaling regulated SATB1 promotes colorectal cancer tumorigenesis and progression. Oncogene 35:1679–1691. doi:10.1038/onc.2015.232

    Article  CAS  PubMed  Google Scholar 

  4. Tu W, Luo M, Wang Z, Yan W, Xia Y, Deng H, He J, Han P, Tian D (2012) Upregulation of SATB1 promotes tumor growth and metastasis in liver cancer. Liver Int 32:1064–1078. doi:10.1111/j.1478-3231.2012.02815.x

    Article  CAS  PubMed  Google Scholar 

  5. Burute M, Gottimukkala K, Galande S (2012) Chromatin organizer SATB1 is an important determinant of T-cell differentiation. Immunol Cell Biol 90:852–859. doi:10.1038/icb.2012.28

    Article  CAS  PubMed  Google Scholar 

  6. Kondo M, Tanaka Y, Kuwabara T, Naito T, Kohwi-Shigematsu T, Watanabe A (2016) SATB1 Plays a critical role in establishment of immune tolerance. J Immunol 196:563–572. doi:10.4049/jimmunol.1501429

    Article  CAS  PubMed  Google Scholar 

  7. Ahlfors H, Limaye A, Elo LL, Tuomela S, Burute M, Gottimukkala KV, Notani D, Rasool O, Galande S, Lahesmaa R (2010) SATB1 dictates expression of multiple genes including IL-5 involved in human T helper cell differentiation. Blood 116:1443–1453. doi:10.1182/blood-2009-11-252205

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Cai S, Han HJ, Kohwi-Shigematsu T (2003) Tissue-specific nuclear architecture and gene expression regulated by SATB1. Nat Genet 34:42–51. doi:10.1038/ng1146

    Article  CAS  PubMed  Google Scholar 

  9. Seo J, Lozano MM, Dudley JP (2005) Nuclear matrix binding regulates SATB1-mediated transcriptional repression. J Biol Chem 280:24600–24609. doi:10.1074/jbc.M414076200

    Article  CAS  PubMed  Google Scholar 

  10. Cai S, Lee CC, Kohwi-Shigematsu T (2006) SATB1 packages densely looped, transcriptionally active chromatin for coordinated expression of cytokine genes. Nat Genet 38:1278–1288. doi:10.1038/ng1913

    Article  CAS  PubMed  Google Scholar 

  11. Kohwi-Shigematsu T, Kohwi Y, Takahashi K, Richards HW, Ayers SD, Han HJ, Cai S (2012) SATB1-mediated functional packaging of chromatin into loops. Methods 58:243–254. doi:10.1016/j.ymeth.2012.06.019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Gong H, Wang Z, Zhao GW, Lv X, Wei GH, Wang L, Liu DP, Liang CC (2009) SATB1 regulates beta-like globin genes through matrix related nuclear relocation of the cluster. Biochem Biophys Res Commun 383:11–15. doi:10.1016/j.bbrc.2009.03.122

    Article  CAS  PubMed  Google Scholar 

  13. Kumar PP, Purbey PK, Ravi DS, Mitra D, Galande S (2005) 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. doi:10.1128/MCB.25.5.1620-1633.2005

    Article  PubMed  PubMed Central  Google Scholar 

  14. Pavan Kumar P, Purbey PK, Sinha CK, Notani D, Limaye A, Jayani RS, Galande S (2006) Phosphorylation of SATB1, a global gene regulator, acts as a molecular switch regulating its transcriptional activity in vivo. Mol Cell 22:231–243. doi:10.1016/j.molcel.2006.03.010

    Article  CAS  PubMed  Google Scholar 

  15. Purbey PK, Singh S, Notani D, Kumar PP, Limaye AS, Galande S (2009) Acetylation-dependent interaction of SATB1 and CtBP1 mediates transcriptional repression by SATB1. Mol Cell Biol 29:1321–1337. doi:10.1128/MCB.00822-08

    Article  CAS  PubMed  Google Scholar 

  16. Kumar PP, Bischof O, Purbey PK, Notani D, Urlaub H, Dejean A, Galande S (2007) Functional interaction between PML and SATB1 regulates chromatin-loop architecture and transcription of the MHC class I locus. Nat Cell Biol 9:45–56. doi:10.1038/ncb1516

    Article  PubMed  Google Scholar 

  17. Zhong S, Muller S, Ronchetti S, Freemont PS, Dejean A, Pandolfi PP (2000) Role of SUMO-1-modified PML in nuclear body formation. Blood 95:2748–2752

    CAS  PubMed  Google Scholar 

  18. Liu Y, van den Berg A, Veenstra R, Rutgers B, Nolte I, van Imhoff G, Visser L, Diepstra A (2013) PML nuclear bodies and SATB1 are associated with HLA class I expression in EBV + Hodgkin lymphoma. PLoS One 8:e72930. doi:10.1371/journal.pone.0072930

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Turner J, Crossley M (2001) The CtBP family: enigmatic and enzymatic transcriptional co-repressors. Bioessays 23:683–690. doi:10.1002/bies.1097

    Article  CAS  PubMed  Google Scholar 

  20. Fujii Y, Kumatori A, Nakamura M (2003) SATB1 makes a complex with p300 and represses gp91(phox) promoter activity. Microbiol Immunol 47:803–811

    Article  CAS  PubMed  Google Scholar 

  21. Gong F, Sun L, Wang Z, Shi J, Li W, Wang S, Han X, Sun Y (2011) The BCL2 gene is regulated by a special AT-rich sequence binding protein 1-mediated long range chromosomal interaction between the promoter and the distal element located within the 3′-UTR. Nucleic Acids Res 39:4640–4652. doi:10.1093/nar/gkr023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Li K, Cai R, Dai BB, Zhang XQ, Wang HJ, Ge SF, Xu WR, Lu J (2007) SATB1 regulates SPARC expression in K562 cell line through binding to a specific sequence in the third intron. Biochem Biophys Res Commun 356:6–12. doi:10.1016/j.bbrc.2007.01.201

    Article  CAS  PubMed  Google Scholar 

  23. Hawkins SM, Kohwi-Shigematsu T, Skalnik DG (2001) 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. doi:10.1074/jbc.M104193200

    Article  CAS  PubMed  Google Scholar 

  24. Luo W, Skalnik DG (1996) CCAAT displacement protein competes with multiple transcriptional activators for binding to four sites in the proximal gp91phox promoter. J Biol Chem 271:18203–18210

    Article  CAS  PubMed  Google Scholar 

  25. Yasui D, Miyano M, Cai S, Varga-Weisz P, Kohwi-Shigematsu T (2002) SATB1 targets chromatin remodelling to regulate genes over long distances. Nature 419:641–645. doi:10.1038/nature01084

    Article  CAS  PubMed  Google Scholar 

  26. Ehret A, Li-Weber M, Frank R, Krammer PH (2001) The effect of HIV-1 regulatory proteins on cellular genes: derepression of the IL-2 promoter by Tat. Eur J Immunol 31:1790–1799. doi:10.1002/1521-4141(200106)31:6<1790::AID-IMMU1790>3.0.CO;2-G

    Article  CAS  PubMed  Google Scholar 

  27. He G, Margolis DM (2002) Counterregulation of chromatin deacetylation and histone deacetylase occupancy at the integrated promoter of human immunodeficiency virus type 1 (HIV-1) by the HIV-1 repressor YY1 and HIV-1 activator Tat. Mol Cell Biol 22:2965–2973

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Dickinson LA, Dickinson CD, Kohwi-Shigematsu T (1997) An atypical homeodomain in SATB1 promotes specific recognition of the key structural element in a matrix attachment region. J Biol Chem 272:11463–11470

    Article  CAS  PubMed  Google Scholar 

  29. Nakagomi K, Kohwi Y, Dickinson LA, Kohwi-Shigematsu T (1994) A novel DNA-binding motif in the nuclear matrix attachment DNA-binding protein SATB1. Mol Cell Biol 14:1852–1860

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Galande S, Dickinson LA, Mian IS, Sikorska M, Kohwi-Shigematsu T (2001) 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. doi:10.1128/MCB.21.16.5591-5604.2001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Purbey PK, Singh S, Kumar PP, Mehta S, Ganesh KN, Mitra D, Galande S (2008) PDZ domain-mediated dimerization and homeodomain-directed specificity are required for high-affinity DNA binding by SATB1. Nucleic Acids Res 36:2107–2122. doi:10.1093/nar/gkm1151

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Wang Z, Yang X, Chu X, Zhang J, Zhou H, Shen Y, Long J (2012) The structural basis for the oligomerization of the N-terminal domain of SATB1. Nucleic Acids Res 40:4193–4202. doi:10.1093/nar/gkr1284

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Wang Z, Yang X, Guo S, Yang Y, Su XC, Shen Y, Long J (2014) Crystal structure of the ubiquitin-like domain-CUT repeat-like tandem of special AT-rich sequence binding protein 1 (SATB1) reveals a coordinating DNA-binding mechanism. J Biol Chem 289:27376–27385. doi:10.1074/jbc.M114.562314

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Notani D, Ramanujam PL, Kumar PP, Gottimukkala KP, Kumar-Sinha C, Galande S (2011) N-terminal PDZ-like domain of chromatin organizer SATB1 contributes towards its function as transcription regulator. J Biosci 36:461–469

    Article  CAS  PubMed  Google Scholar 

  35. Alvarez JD, Yasui DH, Niida H, Joh T, Loh DY, Kohwi-Shigematsu T (2000) The MAR-binding protein SATB1 orchestrates temporal and spatial expression of multiple genes during T-cell development. Genes Dev 14:521–535

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Liu J, Bramblett D, Zhu Q, Lozano M, Kobayashi R, Ross SR, Dudley JP (1997) The matrix attachment region-binding protein SATB1 participates in negative regulation of tissue-specific gene expression. Mol Cell Biol 17:5275–5287

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This study was supported by the State Key Laboratory of Membrane Biology (to H.Z.), the State Key Laboratory of Medicinal Chemical Biology (to H.Z.), 973 Program Grants 2014CB910201 (to J.L.), and National Natural Science Foundation of China Grants 31470755 and 31670758 (to J.L.).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hao Zhou.

Ethics declarations

Conflict of interest

The authors declare no conflict of interests/no competing interests in relation to this work.

Additional information

Minying Zheng and Wancai Xing have contributed equally to this work.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 26186 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zheng, M., Xing, W., Liu, Y. et al. Tetramerization of SATB1 is essential for regulating of gene expression. Mol Cell Biochem 430, 171–178 (2017). https://doi.org/10.1007/s11010-017-2964-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-017-2964-6

Keywords

Navigation