SATB1 (SATB homeobox 1)

2009-06-01   Hunter Richards , Terumi Kohwi-Shigematsu 

Lawrence Berkeley National Laboratory, 1 Cyclotron Rd, Bldg 84-155, University of California, Berkeley, 94720, USA

Identity

HGNC
LOCATION
3p24.3
IMAGE
Atlas 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

Atlas Image

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.

Bibliography

Pubmed IDLast YearTitleAuthors
193862602009SATB1 defines the developmental context for gene silencing by Xist in lymphoma and embryonic cells.Agrelo R et al
107169412000The MAR-binding protein SATB1 orchestrates temporal and spatial expression of multiple genes during T-cell development.Alvarez JD et al
126925532003Tissue-specific nuclear architecture and gene expression regulated by SATB1.Cai S et al
170577182006SATB1 packages densely looped, transcriptionally active chromatin for coordinated expression of cytokine genes.Cai S et al
91110591997An atypical homeodomain in SATB1 promotes specific recognition of the key structural element in a matrix attachment region.Dickinson LA et al
114638402001SATB1 cleavage by caspase 6 disrupts PDZ domain-mediated dimerization, causing detachment from chromatin early in T-cell apoptosis.Galande S et al
183378162008SATB1 reprogrammes gene expression to promote breast tumour growth and metastasis.Han HJ et al
171730412007Functional interaction between PML and SATB1 regulates chromatin-loop architecture and transcription of the MHC class I locus.Kumar PP et al
81147181994A novel DNA-binding motif in the nuclear matrix attachment DNA-binding protein SATB1.Nakagomi K et al
159706962005A nuclear targeting determinant for SATB1, a genome organizer in the T cell lineage.Nakayama Y et al
166308922006Phosphorylation of SATB1, a global gene regulator, acts as a molecular switch regulating its transcriptional activity in vivo.Pavan Kumar P et al
176941752007A distal single nucleotide polymorphism alters long-range regulation of the PU.1 gene in acute myeloid leukemia.Steidl U et al
123749852002SATB1 targets chromatin remodelling to regulate genes over long distances.Yasui D et al
95487131998The 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

Gene IDTranscript IDUniprot
ENSG00000182568ENST00000338745Q01826
ENSG00000182568ENST00000338745A0A024R2H1
ENSG00000182568ENST00000414509C9JLL5
ENSG00000182568ENST00000415069C9JGL9
ENSG00000182568ENST00000417717Q01826
ENSG00000182568ENST00000440737C9JP21
ENSG00000182568ENST00000444341C9J3I0
ENSG00000182568ENST00000450898A0A1D5RMP0
ENSG00000182568ENST00000452260C9IZC5
ENSG00000182568ENST00000454909Q01826
ENSG00000182568ENST00000454909A0A024R2H1
ENSG00000182568ENST00000457005C9J7F3
ENSG00000182568ENST00000475083A0A087WW75
ENSG00000182568ENST00000491519A0A087WW22
ENSG00000182568ENST00000493952H0YN86

Expression (GTEx)

0
5
10
15
20
25
30

Pathways

PathwaySourceExternal ID
Programmed Cell DeathREACTOMER-HSA-5357801
ApoptosisREACTOMER-HSA-109581
Apoptotic execution phaseREACTOMER-HSA-75153
Apoptotic cleavage of cellular proteinsREACTOMER-HSA-111465

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
183378162008SATB1 reprogrammes gene expression to promote breast tumour growth and metastasis.213
123749852002SATB1 targets chromatin remodelling to regulate genes over long distances.164
171730412007Functional interaction between PML and SATB1 regulates chromatin-loop architecture and transcription of the MHC class I locus.100
201262582010Global regulator SATB1 recruits beta-catenin and regulates T(H)2 differentiation in Wnt-dependent manner.86
166308922006Phosphorylation of SATB1, a global gene regulator, acts as a molecular switch regulating its transcriptional activity in vivo.63
203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62
218417852011Repression of the genome organizer SATB1 in regulatory T cells is required for suppressive function and inhibition of effector differentiation.62
227716152013Genome organizing function of SATB1 in tumor progression.55
208116792010SATB1 is an independent prognostic marker for gastric cancer in a Chinese population.42
156184652005SATB1 family protein expressed during early erythroid differentiation modifies globin gene expression.39

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