SATB1 (SATB homeobox 1)
2009-06-01 Hunter Richards  , Terumi Kohwi-Shigematsu   AffiliationLawrence Berkeley National Laboratory, 1 Cyclotron Rd, Bldg 84-155, University of California, Berkeley, 94720, USA
Identity
HGNC
LOCATION
3p24.3
IMAGE

LOCUSID
ALIAS
DEFDA,KTZSL
FUSION GENES
DNA/RNA
Description
The gene encompasses 93 kb of genomic DNA in mouse and 91 kb in humans both of which comprise 11 exons, 10 of which are coding.
Transcription
GenBank references two mRNA transcript variants in humans: #1 is 5423 bp in length and #2 is 3908 bp. They have identical 3 UTRs whereas variant #1 has a longer 5 UTR. GenBank references one mRNA transcript in mouse: 2922 bp in length.
Proteins

Description
SATB1 is a 763 amino acid protein (~86 kDa molecular weight, migrates as 103kDa on SDS gels) containing six described domains: nuclear localization signal (NLS), PDZ, BUR-binding domain, two Cut repeats (CUT1 and CUT2), and homeodomain (HD). The PDZ domain is a protein-protein interaction module found mostly in signaling proteins. The BUR (Base Unpairing Region) domain is the module responsible for specific recognition of the BURs as opposed to any AT-rich sequence motif. The CUT domain is a DNA-binding motif. The BUR-binding domain includes CUT1 and part of the CUT2 domain. Homeodomains are DNA-binding motifs typically found in transcription factors. Together with the BUR domain and the HD domain, SATB1 confers specific binding with high affinity to the core unwinding elements of BURs. SATB1 is highly conserved between vertebrates.
Expression
SATB1 mRNA is expressed abundantly in thymocytes. It is also detected in multiple other progenitor cells and brain neurons.
Localisation
Nuclear.
Function
SATB1 was identified by virtue of its high affinity and specificity to a DNA probe containing a nucleation site for base-unpairing, a phenomena whereby these sites become continuously unpaired under negative helical strain. Evidence suggests these base unpairing regions (BURs) mark the genome as essential components of chromosomes for tissue-specific gene expression and chromatin accessibility. SATB1 localization is nuclear exhibiting a cage- or honeycomb-like network distribution in thymocytes that is partially resistant to high-salt extraction and is excluded from the heterochromatin compartment. SATB1 tethers its target genes onto the SATB1 network via BURs which reside within the gene loci, and assembles them with chromatin remodeling and histone modification enzymes which SATB1 recruits. In this manner, SATB1 establishes a region-specific epigenetic status and proper nucleosomal positioning at the SATB1 target gene loci. SATB1 is essential for T-cell activation by controlling chromatin looping events, thus bringing remote cytokine genes together for simultaneous induction of these genes. SATB1 has been reported to interact with: CtBP1, SUMO-1, PIAS, Ubc9, PML, HDAC1, p300, RPB11, SNF2H (ISWI), Mi-2, MTA-2, and ACF1.
Homology
SATB1 has 59.5% identity to SATB2 (mouse protein sequence; 46.6% for the human protein sequence).
Mutations
Note
None identified.
Implicated in
Entity name
Breast cancer
Prognosis
In breast cancer SATB1 protein expression levels have high prognostic significance independent of lymph node status.
Oncogenesis
In aggressive human breast cancer cell lines and in tissue samples from patients with aggressive breast tumors SATB1 protein is highly expressed. Ectopic expression of SATB1 in non-aggressive breast cancer cells induces metastasis, whereas depletion of SATB1 in highly-aggressive breast cancer cells reverses their metastatic capabilities and other tumorigenic characteristics.
Entity name
Acute myeloid leukemia (AML), and lymphoma
Oncogenesis
SATB1 positively regulates the PU.1 gene by binding to its distal enhancer. PU.1 is a transcription factor important for B-cell and myeloid development. A single mutation in the distal enhancer dramatically reduces binding by SATB1. SATB1 was found to be an important factor of Xist (X-inactivation specific transcript) silencing in thymic lymphoma cells, potentially by stabilizing Xist transcripts.
Breakpoints
Note
None known.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 19386260 | 2009 | SATB1 defines the developmental context for gene silencing by Xist in lymphoma and embryonic cells. | Agrelo R et al |
| 10716941 | 2000 | The MAR-binding protein SATB1 orchestrates temporal and spatial expression of multiple genes during T-cell development. | Alvarez JD et al |
| 12692553 | 2003 | Tissue-specific nuclear architecture and gene expression regulated by SATB1. | Cai S et al |
| 17057718 | 2006 | SATB1 packages densely looped, transcriptionally active chromatin for coordinated expression of cytokine genes. | Cai S et al |
| 9111059 | 1997 | An atypical homeodomain in SATB1 promotes specific recognition of the key structural element in a matrix attachment region. | Dickinson LA et al |
| 11463840 | 2001 | SATB1 cleavage by caspase 6 disrupts PDZ domain-mediated dimerization, causing detachment from chromatin early in T-cell apoptosis. | Galande S et al |
| 18337816 | 2008 | SATB1 reprogrammes gene expression to promote breast tumour growth and metastasis. | Han HJ et al |
| 17173041 | 2007 | Functional interaction between PML and SATB1 regulates chromatin-loop architecture and transcription of the MHC class I locus. | Kumar PP et al |
| 8114718 | 1994 | A novel DNA-binding motif in the nuclear matrix attachment DNA-binding protein SATB1. | Nakagomi K et al |
| 15970696 | 2005 | A nuclear targeting determinant for SATB1, a genome organizer in the T cell lineage. | Nakayama Y et al |
| 16630892 | 2006 | Phosphorylation of SATB1, a global gene regulator, acts as a molecular switch regulating its transcriptional activity in vivo. | Pavan Kumar P et al |
| 17694175 | 2007 | A distal single nucleotide polymorphism alters long-range regulation of the PU.1 gene in acute myeloid leukemia. | Steidl U et al |
| 12374985 | 2002 | SATB1 targets chromatin remodelling to regulate genes over long distances. | Yasui D et al |
| 9548713 | 1998 | 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. | de Belle I et al |
Other Information
Locus ID:
NCBI: 6304
MIM: 602075
HGNC: 10541
Ensembl: ENSG00000182568
Variants:
dbSNP: 6304
ClinVar: 6304
TCGA: ENSG00000182568
COSMIC: SATB1
RNA/Proteins
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 37932931 | 2024 | TOX, TWIST1, STAT4, and SATB1 protein expressions in early-stage mycosis fungoides. | 0 |
| 37985573 | 2024 | Long Non-Coding RNA ANRIL Regulates Inflammatory Factor Expression in Ulcerative Colitis Via the miR-191-5p/SATB1 Axis. | 0 |
| 38150791 | 2024 | Long non-coding RNA LINC00491 accelerates head and neck squamous cell carcinoma progression through regulating miR-508-3p/SATB1 axis and activating Wnt signaling pathway. | 0 |
| 38385627 | 2024 | SATB1 mediated tumor colonization and β-catenin nuclear localization are associated with colorectal cancer progression. | 0 |
| 37932931 | 2024 | TOX, TWIST1, STAT4, and SATB1 protein expressions in early-stage mycosis fungoides. | 0 |
| 37985573 | 2024 | Long Non-Coding RNA ANRIL Regulates Inflammatory Factor Expression in Ulcerative Colitis Via the miR-191-5p/SATB1 Axis. | 0 |
| 38150791 | 2024 | Long non-coding RNA LINC00491 accelerates head and neck squamous cell carcinoma progression through regulating miR-508-3p/SATB1 axis and activating Wnt signaling pathway. | 0 |
| 38385627 | 2024 | SATB1 mediated tumor colonization and β-catenin nuclear localization are associated with colorectal cancer progression. | 0 |
| 36495733 | 2023 | Overexpression of SATB1 correlates with epithelial-mesenchymal transition and lymphatic metastasis in gastric cancer. | 0 |
| 36987811 | 2023 | SATB1 Chromatin Loops Regulate Megakaryocyte/Erythroid Progenitor Expansion by Facilitating HSP70 and GATA1 Induction. | 0 |
| 37000624 | 2023 | SATB1 regulates 3D genome architecture in T cells by constraining chromatin interactions surrounding CTCF-binding sites. | 4 |
| 36495733 | 2023 | Overexpression of SATB1 correlates with epithelial-mesenchymal transition and lymphatic metastasis in gastric cancer. | 0 |
| 36987811 | 2023 | SATB1 Chromatin Loops Regulate Megakaryocyte/Erythroid Progenitor Expansion by Facilitating HSP70 and GATA1 Induction. | 0 |
| 37000624 | 2023 | SATB1 regulates 3D genome architecture in T cells by constraining chromatin interactions surrounding CTCF-binding sites. | 4 |
| 35113413 | 2022 | Expression of SATB1 is a prognostic indicator for survival in diffuse large B-cell lymphoma patients. | 0 |
Citation
Hunter Richards ; Terumi Kohwi-Shigematsu
SATB1 (SATB homeobox 1)
Atlas Genet Cytogenet Oncol Haematol. 2009-06-01
Online version: http://atlasgeneticsoncology.org/gene/44225/satb1
