2l1p

Structural highlights

Function

[SATB1_HUMAN] Crucial silencing factor contributing to the initiation of X inactivation mediated by Xist RNA that occurs during embryogenesis and in lymphoma (By similarity). Binds to DNA at special AT-rich sequences, the consensus SATB1-binding sequence (CSBS), at nuclear matrix- or scaffold-associated regions. Thought to recognize the sugar-phosphate structure of double-stranded DNA. Transcriptional repressor controlling nuclear and viral gene expression in a phosphorylated and acetylated status-dependent manner, by binding to matrix attachment regions (MARs) of DNA and inducing a local chromatin-loop remodeling. Acts as a docking site for several chromatin remodeling enzymes (e.g. PML at the MHC-I locus) and also by recruiting corepressors (HDACs) or coactivators (HATs) directly to promoters and enhancers. Modulates genes that are essential in the maturation of the immune T-cell CD8SP from thymocytes. Required for the switching of fetal globin species, and beta- and gamma-globin genes regulation during erythroid differentiation. Plays a role in chromatin organization and nuclear architecture during apoptosis. Interacts with the unique region (UR) of cytomegalovirus (CMV). Alu-like motifs and SATB1-binding sites provide a unique chromatin context which seems preferentially targeted by the HIV-1 integration machinery. Moreover, HIV-1 Tat may overcome SATB1-mediated repression of IL2 and IL2RA (interleukin) in T-cells by binding to the same domain than HDAC1. Delineates specific epigenetic modifications at target gene loci, directly up-regulating metastasis-associated genes while down-regulating tumor-suppressor genes. Reprograms chromatin organization and the transcription profiles of breast tumors to promote growth and metastasis.^{[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

1. ↑ Dickinson LA, Joh T, Kohwi Y, Kohwi-Shigematsu T. A tissue-specific MAR/SAR DNA-binding protein with unusual binding site recognition. Cell. 1992 Aug 21;70(4):631-45. PMID:1505028
2. ↑ Dickinson LA, Dickinson CD, Kohwi-Shigematsu T. An atypical homeodomain in SATB1 promotes specific recognition of the key structural element in a matrix attachment region. J Biol Chem. 1997 Apr 25;272(17):11463-70. PMID:9111059
3. ↑ de Belle I, Cai S, Kohwi-Shigematsu T. The genomic sequences bound to special AT-rich sequence-binding protein 1 (SATB1) in vivo in Jurkat T cells are tightly associated with the nuclear matrix at the bases of the chromatin loops. J Cell Biol. 1998 Apr 20;141(2):335-48. PMID:9548713
4. ↑ Case SS, Huber P, Lloyd JA. The gammaPE complex contains both SATB1 and HOXB2 and has positive and negative roles in human gamma-globin gene regulation. DNA Cell Biol. 1999 Nov;18(11):805-17. PMID:10595394 doi:10.1089/104454999314809
5. ↑ Galande S, Dickinson LA, Mian IS, 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. 2001 Aug;21(16):5591-604. PMID:11463840 doi:10.1128/MCB.21.16.5591-5604.2001
6. ↑ Yasui D, Miyano M, Cai S, Varga-Weisz P, Kohwi-Shigematsu T. SATB1 targets chromatin remodelling to regulate genes over long distances. Nature. 2002 Oct 10;419(6907):641-5. PMID:12374985 doi:10.1038/nature01084
7. ↑ Cai S, Han HJ, Kohwi-Shigematsu T. Tissue-specific nuclear architecture and gene expression regulated by SATB1. Nat Genet. 2003 May;34(1):42-51. PMID:12692553 doi:10.1038/ng1146
8. ↑ Wen J, Huang S, Rogers H, Dickinson LA, Kohwi-Shigematsu T, Noguchi CT. SATB1 family protein expressed during early erythroid differentiation modifies globin gene expression. Blood. 2005 Apr 15;105(8):3330-9. Epub 2004 Dec 23. PMID:15618465 doi:10.1182/blood-2004-08-2988
9. ↑ Kumar PP, Purbey PK, Ravi DS, 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. 2005 Mar;25(5):1620-33. PMID:15713622 doi:25/5/1620
10. ↑ Sun Y, Wang T, Su Y, Yin Y, Xu S, Ma C, Han X. The behavior of SATB1, a MAR-binding protein, in response to apoptosis stimulation. Cell Biol Int. 2006 Mar;30(3):244-7. Epub 2005 Dec 27. PMID:16377216 doi:10.1016/j.cellbi.2005.10.025
11. ↑ Pavan Kumar P, Purbey PK, Sinha CK, Notani D, Limaye A, Jayani RS, Galande S. Phosphorylation of SATB1, a global gene regulator, acts as a molecular switch regulating its transcriptional activity in vivo. Mol Cell. 2006 Apr 21;22(2):231-43. PMID:16630892 doi:10.1016/j.molcel.2006.03.010
12. ↑ Kumar PP, Mehta S, Purbey PK, Notani D, Jayani RS, Purohit HJ, Raje DV, Ravi DS, Bhonde RR, Mitra D, Galande S. SATB1-binding sequences and Alu-like motifs define a unique chromatin context in the vicinity of human immunodeficiency virus type 1 integration sites. J Virol. 2007 Jun;81(11):5617-27. Epub 2007 Mar 21. PMID:17376900 doi:10.1128/JVI.01405-06
13. ↑ Kumar PP, Bischof O, Purbey PK, Notani D, Urlaub H, Dejean A, Galande S. Functional interaction between PML and SATB1 regulates chromatin-loop architecture and transcription of the MHC class I locus. Nat Cell Biol. 2007 Jan;9(1):45-56. Epub 2006 Dec 17. PMID:17173041 doi:10.1038/ncb1516
14. ↑ Han HJ, Russo J, Kohwi Y, Kohwi-Shigematsu T. SATB1 reprogrammes gene expression to promote breast tumour growth and metastasis. Nature. 2008 Mar 13;452(7184):187-93. doi: 10.1038/nature06781. PMID:18337816 doi:10.1038/nature06781
15. ↑ Gong H, Wang Z, Zhao GW, Lv X, Wei GH, Wang L, Liu DP, Liang CC. SATB1 regulates beta-like globin genes through matrix related nuclear relocation of the cluster. Biochem Biophys Res Commun. 2009 May 22;383(1):11-5. doi:, 10.1016/j.bbrc.2009.03.122. Epub 2009 Mar 28. PMID:19332023 doi:10.1016/j.bbrc.2009.03.122
16. ↑ Cai R, Xu W, Dai B, Cai X, Xu R, Lu J. SATB1 binds an intronic MAR sequence in human PI3kgamma in vitro. Mol Biol Rep. 2010 Mar;37(3):1461-5. doi: 10.1007/s11033-009-9538-y. Epub 2009, May 10. PMID:19430959 doi:10.1007/s11033-009-9538-y
17. ↑ Purbey PK, Singh S, Notani D, Kumar PP, Limaye AS, Galande S. Acetylation-dependent interaction of SATB1 and CtBP1 mediates transcriptional repression by SATB1. Mol Cell Biol. 2009 Mar;29(5):1321-37. doi: 10.1128/MCB.00822-08. Epub 2008 Dec, 22. PMID:19103759 doi:10.1128/MCB.00822-08
18. ↑ Wang L, Di LJ, Lv X, Zheng W, Xue Z, Guo ZC, Liu DP, Liang CC. Inter-MAR association contributes to transcriptionally active looping events in human beta-globin gene cluster. PLoS One. 2009;4(2):e4629. doi: 10.1371/journal.pone.0004629. Epub 2009 Feb 27. PMID:19247486 doi:10.1371/journal.pone.0004629