| Structural highlights
Function
[SATB1_MOUSE] 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 (By similarity). Crucial silencing factor contributing to the initiation of X inactivation mediated by Xist RNA that occurs during embryogenesis and in lymphoma. 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 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.[1] [2] [3] [4] [5] [6] [7] [8] [9]
Publication Abstract from PubMed
SATB1 is essential for T-cell development and growth and metastasis of multitype tumors and acts as a global chromatin organizer and gene expression regulator. The DNA binding ability of SATB1 plays vital roles in its various biological functions. We report the crystal structure of the N-terminal module of SATB1. Interestingly, this module contains a ubiquitin-like domain (ULD) and a CUT repeat-like (CUTL) domain (ULD-CUTL tandem). Detailed biochemical experiments indicate that the N terminus of SATB1 (residues 1-248, SATB1((1-248))), including the extreme 70 N-terminal amino acids, and the ULD-CUTL tandem bind specifically to DNA targets. Our results show that the DNA binding ability of full-length SATB1 requires the contribution of the CUTL domain, as well as the CUT1-CUT2 tandem domain and the homeodomain. These findings may reveal a multiple-domain-coordinated mechanism whereby SATB1 recognizes DNA targets.
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.,Wang Z, Yang X, Guo S, Yang Y, Su XC, Shen Y, Long J J Biol Chem. 2014 Oct 3;289(40):27376-85. doi: 10.1074/jbc.M114.562314. Epub 2014, Aug 14. PMID:25124042[10]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Alvarez JD, Yasui DH, Niida H, Joh T, Loh DY, Kohwi-Shigematsu T. The MAR-binding protein SATB1 orchestrates temporal and spatial expression of multiple genes during T-cell development. Genes Dev. 2000 Mar 1;14(5):521-35. PMID:10716941
- ↑ 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
- ↑ 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
- ↑ Nie H, Maika SD, Tucker PW, Gottlieb PD. A role for SATB1, a nuclear matrix association region-binding protein, in the development of CD8SP thymocytes and peripheral T lymphocytes. J Immunol. 2005 Apr 15;174(8):4745-52. PMID:15814699
- ↑ Cai S, Lee CC, Kohwi-Shigematsu T. SATB1 packages densely looped, transcriptionally active chromatin for coordinated expression of cytokine genes. Nat Genet. 2006 Nov;38(11):1278-88. Epub 2006 Oct 22. PMID:17057718 doi:http://dx.doi.org/10.1038/ng1913
- ↑ Nie H, Yao X, Maika SD, Tucker PW. SATB1 is required for CD8 coreceptor reversal. Mol Immunol. 2008 Nov;46(1):207-11. doi: 10.1016/j.molimm.2008.07.007. Epub 2008 , Aug 21. PMID:18722016 doi:http://dx.doi.org/10.1016/j.molimm.2008.07.007
- ↑ 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
- ↑ Agrelo R, Souabni A, Novatchkova M, Haslinger C, Leeb M, Komnenovic V, Kishimoto H, Gresh L, Kohwi-Shigematsu T, Kenner L, Wutz A. SATB1 defines the developmental context for gene silencing by Xist in lymphoma and embryonic cells. Dev Cell. 2009 Apr;16(4):507-16. doi: 10.1016/j.devcel.2009.03.006. PMID:19386260 doi:http://dx.doi.org/10.1016/j.devcel.2009.03.006
- ↑ Liu J, Bramblett D, Zhu Q, Lozano M, Kobayashi R, Ross SR, Dudley JP. The matrix attachment region-binding protein SATB1 participates in negative regulation of tissue-specific gene expression. Mol Cell Biol. 1997 Sep;17(9):5275-87. PMID:9271405
- ↑ Wang Z, Yang X, Guo S, Yang Y, Su XC, Shen Y, Long J. 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. 2014 Oct 3;289(40):27376-85. doi: 10.1074/jbc.M114.562314. Epub 2014, Aug 14. PMID:25124042 doi:http://dx.doi.org/10.1074/jbc.M114.562314
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