Disease relevance of SATB1

• Moreover, binding of SATB1 to the mouse mammary tumor virus (MMTV) promoter region dramatically affects the tissue-specific transcription of this retrovirus [1].
• 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 [2].
• Erythroid differentiation of human erythroleukemia K562 cells by hemin simultaneously increases gamma-globin and down-regulates SATB1 family protein and epsilon-globin gene expression [3].
• Difficulties with previous assay systems prompted us to develop retroviral vectors to assess effects of different SATB1 domains on expression of MMTV proviruses or integrated reporter genes [4].
• In human breast cancer SK-BR-3 cells that do not express SATB1, at least one such sequence was found not anchored onto the nuclear matrix [5].

Psychiatry related information on SATB1

• SATB1 facilitates the nuclear localization of rp3, whereas rp3 and dynein motor activity are not essential for nuclear accumulation of SATB1 [6].

High impact information on SATB1

• A new study shows that during transcription, the T(H)2 interleukin gene cluster is organized into several small chromatin loops connected at their base by the protein SATB1 [7].
• SATB1 (special AT-rich sequence binding protein 1) organizes cell type-specific nuclear architecture by anchoring specialized DNA sequences and recruiting chromatin remodeling factors to control gene transcription [8].
• SATB1 recruits the histone deacetylase contained in the NURD chromatin remodelling complex to a SATB1-bound site in the IL-2Ralpha locus, and mediates the specific deacetylation of histones in a large domain within the locus [9].
• Ablation of SATB1 by gene targeting results in temporal and spatial mis-expression of numerous genes and arrested T-cell development, suggesting that SATB1 is a cell-type specific global gene regulator [9].
• SATB1 ('special AT-rich sequence binding 1'), a protein found predominantly in thymocytes, regulates genes by folding chromatin into loop domains, tethering specialized DNA elements to an SATB1 network structure [9].

Biological context of SATB1

• Because of the tissue and cell type distribution of SATB1 and CDP, we propose that the SATB1-to-CDP ratio in different tissues is a novel mechanism for homeoproteins to control gene expression and differentiation in mammals [1].
• CDP overexpression also elevated MMTV long terminal repeat reporter gene activity in transient-transfection assays, a result consistent with neutralization of the SATB1 repressor function in T cells [1].
• CDP overexpression in cultured T cells led to a loss of detectable SATB1 binding to the MMTV promoter region, as measured by gel shift experiments [1].
• Furthermore, Tat competitively displaces HDAC1 that is bound to SATB1, leading to increased acetylation of the promoters in vivo [2].
• By gel shift analysis we identified two strong SATB1 binding sites, located 4.5 kb apart, in strong MARs [10].

Anatomical context of SATB1

• SATB1 is very abundant in certain tissues, particularly thymus, whereas CDP is relatively ubiquitous, except in certain terminally differentiated cell types [1].
• In K562 cells SATB1 family protein forms a complex with CREB-binding protein (CBP) important in transcriptional activation [3].
• Here we show SATB1 family protein induction during early human adult erythroid progenitor cell differentiation concomitant with epsilon-globin expression [3].
• Wild-type SATB1 localized to the soluble nuclear, chromatin, and nuclear matrix fractions [4].
• To further understand the functional role of MAR-binding proteins during apoptosis we investigated the relationship of the behavior of SATB1 and the collapse of nuclear architecture in Jurkat cells with immunostaining and Western blot analysis [11].

Associations of SATB1 with chemical compounds

• Antibody ablation, distamycin inhibition of binding, renaturation and competition experiments, and tissue distribution data all confirmed that the NBP complex contained SATB1 [12].

Physical interactions of SATB1

• Identification of a candidate regulatory region in the human CD8 gene complex by colocalization of DNase I hypersensitive sites and matrix attachment regions which bind SATB1 and GATA-3 [10].
• Chromatin immunoprecipitation using anti-SATB1 anti-body shows selective binding in vivo in the beta-globin cluster to the hypersensitive site 2 (HS2) in the locus control region (LCR) and to the epsilon-globin promoter [3].
• Nuclear matrix binding regulates SATB1-mediated transcriptional repression [4].
• The nuclear matrix attachment DNA (MAR) binding protein SATB1 is a sequence context-specific binding protein that binds in the minor groove, making virtually no contact with the DNA bases [13].
• The matrix attachment region-binding protein SATB1 interacts with multiple elements within the gp91phox promoter and is down-regulated during myeloid differentiation [14].

Regulatory relationships of SATB1

• SATB1 family protein expressed during early erythroid differentiation modifies globin gene expression [3].
• In addition, SATB1 bound EEGS chromatin and promoted Tal1/SCL EEGS-dependent repression [15].
• SATB1 regulates SPARC expression in K562 cell line through binding to a specific sequence in the third intron [16].

Other interactions of SATB1

• To further establish the importance of this region, we obtained 19 kb of sequence and screened for potential binding sites for the MAR-binding protein, SATB1, and for GATA-3, both of which are critical for T cell development [10].
• The homeoproteins CCAAT displacement protein (CDP) and special AT-rich sequence binding protein 1 (SATB1) have been shown to bind to nuclear matrix-associated regions and to act as repressors of many cellular genes [1].
• SATB1 binds to the nuclear matrix attachment regions of DNA, where it recruits histone deacetylase and represses transcription through a local chromatin remodeling [17].
• Here we show that SATB1 targets chromatin remodelling to the IL-2Ralpha ('interleukin-2 receptor alpha') gene, which is ectopically transcribed in SATB1 null thymocytes [9].
• A yeast two-hybrid screen of a Jurkat (T cell) derived cDNA library, using SATB1 (a matrix attachment region binding protein) as the bait, yielded four independent isolates of a novel variant of the DNA directed RNA polymerase II, subunit 11 (RPB11) [18].

Analytical, diagnostic and therapeutic context of SATB1

• Association of purified SATB1 and CDP in vitro resulted in the inability of each protein to bind to DNA in gel retardation assays [1].
• Far-Western blotting detected interaction of SATB1 and CDP in several different tissue extracts [1].
• By an NMR chemical shift perturbation analysis and by surface plasmon resonance analyses of SATB1 mutant proteins, an interface for DNA binding was revealed to be located at the third helix and the surrounding regions [17].
• Assignment of SATB1 to human chromosome band 3p23 by in situ hybridization [19].
• SATB1 mRNA was identified in K562 cells, and reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated its transcript in several other hematopoietic lines [20].

References