| 1994 |
SATB1 binds DNA at matrix attachment regions (MARs) in the minor groove, making virtually no contact with DNA bases. A 150-amino-acid polypeptide constitutes the binding domain, and a novel DNA-binding motif requires the concomitant presence of both N- and C-terminal ends of the binding domain for full activity. |
Deletion mutagenesis, DNA-binding assays, cloning of mouse SATB1 cDNA |
Molecular and cellular biology |
High |
8114718
|
| 1999 |
SATB1 physically interacts with the homeoprotein CDP (CCAAT displacement protein) through its DNA-binding domain; this interaction is mutual (CDP interacts with three of four SATB1 DNA-binding domains), prevents each protein from binding DNA, and functionally antagonizes SATB1-mediated repression of the MMTV promoter in T cells. |
GST pull-down, reciprocal co-immunoprecipitation from nuclear extracts, far-Western blotting, gel retardation assay, transient-transfection reporter assay |
Molecular and cellular biology |
High |
10373541
|
| 2000 |
SATB1-null mice show severe defects in T-cell development with multiple gene deregulation, demonstrating that SATB1 acts as a global orchestrator of temporal and spatial gene expression during T-cell development, including repression of IL-2Rα and IL-7Rα at inappropriate stages. |
SATB1-null mouse generation, flow cytometry, gene expression profiling of 589 genes |
Genes & development |
High |
10716941
|
| 2005 |
Nuclear matrix binding by SATB1 is required for transcriptional repression: a nuclear matrix targeting sequence (NMTS) spanning amino acids 224–278 is needed for SATB1 localization to the nuclear matrix, and deletion of the NMTS abrogates SATB1-mediated repression of integrated MMTV proviruses without affecting DNA binding. |
SATB1 deletion constructs, nuclear fractionation, retroviral reporter gene assay, GFP fusion localization |
The Journal of biological chemistry |
High |
15851481
|
| 2006 |
On TH2 cell activation, SATB1 folds the 200-kb TH2 cytokine locus (Il5, Il4, Il13) into densely looped chromatin anchored at SATB1 binding sites, recruits Brg1, GATA3, STAT6, c-Maf, and RNA polymerase II across the locus, and is required for cytokine gene expression; RNAi-mediated knockdown of SATB1 abolishes both loop compaction and cytokine induction. |
RNAi knockdown, chromosome conformation capture/looping assays, ChIP for histone modifications and transcription factors, RNA analysis |
Nature genetics |
High |
17057718
|
| 2008 |
SATB1 is sumoylated at lysine-744 by SUMO-1 with Ubc9 and PIAS family members acting as E2 and E3 enzymes; sumoylation targets SATB1 to promyelocytic leukemia nuclear bodies and is required for subsequent caspase cleavage of SATB1. |
Yeast two-hybrid screen, overexpression of SUMO/PIAS in Jurkat cells, site-directed mutagenesis (K744R), in-frame SUMO fusion rescue, immunofluorescence to PML bodies |
The Journal of biological chemistry |
High |
18408014
|
| 2008 |
SATB1 forms a repressor complex with CtBP1 via the PVPLS motif in its PDZ-like domain; PKC-mediated or ionomycin/LiCl-induced acetylation of SATB1 disrupts CtBP1 interaction, reduces CtBP1 and HDAC1 occupancy at SATB1 binding sites (IL-2 and c-Myc promoters), and derepresses target gene expression. |
Co-immunoprecipitation, ChIP, site-directed mutagenesis of PVPLS motif, gene expression profiling with SATB1/CtBP1 siRNA knockdown |
Molecular and cellular biology |
High |
19103759
|
| 2009 |
SATB1 is an essential silencing factor for Xist-mediated gene silencing: loss of SATB1 in lymphoma cells abolishes Xist silencing function; ectopic expression of SATB1 or SATB2 in embryonic fibroblasts (which normally cannot support X inactivation initiation) enables gene silencing by Xist. |
SATB1 loss-of-function in lymphoma model, viral SATB1/SATB2 expression in fibroblasts, Xist localization by FISH, gene silencing assays |
Developmental cell |
High |
19386260
|
| 2009 |
Satb1-null ES cells show impaired differentiation and elevated expression of pluripotency factors (Nanog, Klf4, Tbx3); Satb1 and Satb2 both bind the Nanog locus in vivo and have opposing effects, as Satb1/Satb2 double knockout cells show near-normal differentiation. |
Satb1−/− ES cell analysis, ChIP for Satb1 binding to Nanog locus, gene expression profiling, cell fusion reprogramming assay |
Genes & development |
High |
19933152
|
| 2010 |
SATB1 interacts with β-catenin and recruits it (along with p300 acetyltransferase) to SATB1 genomic binding sites including the GATA3 promoter; this interaction promotes TH2 lineage commitment and is Wnt-signaling dependent. Wnt inhibition (Dkk1) or β-catenin knockdown reduces TH2 cytokine expression. |
Co-immunoprecipitation, ChIP, gene expression profiling, siRNA knockdown of SATB1 and β-catenin, Wnt inhibitor treatment |
PLoS biology |
High |
20126258
|
| 2010 |
SATB1 is phosphorylated by protein kinase C (PKC) at serine 185 in vivo; this phosphorylation enhances SATB1 association with HDAC1 corepressor and promotes transcriptional repression at MAR-linked target genes. |
In vitro kinase assay, in vivo immunoprecipitation after PKC activation, PKC inhibitor treatment, MAR-linked reporter assay |
Methods in molecular biology |
Medium |
20694677
|
| 2011 |
Satb1 binds genomic loci of multiple immediate-early genes (Fos, Fosb, Egr1, Egr2, Arc, Bdnf) in cortical neurons; Satb1-null mice show altered timing and levels of IEG expression during postnatal cortical development and reduced dendritic spine density in cortical pyramidal neurons. |
ChIP for Satb1 at IEG loci, analysis of Satb1-null mouse cortical neurons, dendritic spine density quantification, organotypic culture stimulation |
Molecular and cellular biology |
High |
22064485
|
| 2011 |
SATB1 deficiency in Sézary cells causes apoptosis resistance by failing to activate FasL/CD95L transcription; retroviral restoration of SATB1 in Sézary cells triggers spontaneous cell death, sensitizes cells to activation-induced cell death, activates caspase-8 and caspase-3, and increases endogenous FasL expression. |
Retroviral gene transduction, apoptosis assays, caspase activation analysis, mRNA/protein quantification |
Blood |
Medium |
21270445
|
| 2013 |
Satb1 directs hematopoietic stem cell (HSC) differentiation toward the lymphoid lineage: Satb1-deficient HSCs fail lymphopoiesis in culture and in vivo reconstitution; forced Satb1 expression in HSCs and ES cells robustly promotes lymphocyte differentiation. Reduced Satb1 in aged HSCs correlates with compromised lymphopoietic potential restored by forced Satb1 expression. |
Satb1-knockout mouse, bone marrow transplantation, retroviral Satb1 transduction of HSCs and ES cells, gene expression profiling |
Immunity |
High |
23791645
|
| 2013 |
SATB1 directly regulates p21 transcription in a p53-independent manner in CD30+ lymphoma cells; SATB1 silencing causes G1 cell cycle arrest via p21 activation, demonstrated by ChIP, luciferase assays, and mutational analysis of the p21 promoter. |
ChIP, luciferase reporter assay, mutational analysis of p21 promoter, siRNA knockdown with cell cycle analysis |
Blood |
High |
24747435
|
| 2015 |
SATB1 is required for formation of ON dendritic arbors in ooDSGCs of mouse retina; it regulates expression of homophilic adhesion molecule Contactin 5 (Cntn5), which together with co-receptor Caspr4 mediates branch-specific homophilic interactions with interneurons required for ON dendritic fasciculation. |
Satb1 mutant mouse analysis, electrophysiology, in situ hybridization/immunofluorescence, Cntn5 conditional knockout, morphological quantification |
Neuron |
High |
28781169
|
| 2015 |
HuD RNA-binding protein promotes neuronal differentiation of neural stem/progenitor cells by stabilizing SATB1 mRNA; SATB1 in turn transcriptionally activates HuD, forming a positive feedback loop, with NeuroD1 as a direct downstream transcriptional target of SATB1. |
RNAi knockdown, overexpression rescue experiments, mRNA stability assay, promoter-binding assay |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
26305964
|
| 2015 |
SATB1 binds the Notch1 promoter in dendritic cells, activating Notch1 expression; Notch1 then drives RBPJ occupancy of the H2-Ab1 (MHC II) promoter to activate MHC class II transcription. Satb1 conditional knockout impairs conventional DC differentiation. |
Conditional knockout mouse, ChIP for SATB1 at Notch1 promoter, RBPJ ChIP at H2-Ab1 promoter, DC differentiation assays |
Cell reports |
High |
26876172
|
| 2016 |
Satb1-dependent activation of Treg-specific super-enhancers (Treg-SEs) in Treg precursor cells is required for expression of Foxp3 and other Treg signature genes; T cell-specific Satb1 deficiency impairs Treg-SE activation and causes autoimmunity due to Treg deficiency. |
T cell-specific Satb1 conditional knockout, H3K27ac ChIP-seq to identify super-enhancers, gene expression analysis, autoimmunity phenotyping |
Nature immunology |
High |
27992401
|
| 2017 |
Satb1 recruits the NuRD (nucleosome remodeling deacetylase) complex to Pdcd1 (PD-1) regulatory regions to epigenetically repress PD-1 expression in T cells; tumor-derived TGF-β suppresses Satb1 expression via Smad binding to the Satb1 promoter, and Smad proteins compete with the Satb1-NuRD complex for binding to Pdcd1 enhancers. |
Satb1-deficient T cells, ChIP for NuRD complex at Pdcd1 locus, Smad binding assay at Satb1 promoter and Pdcd1 enhancers, competition assay |
Immunity |
High |
28099864
|
| 2017 |
In post-selection thymocytes, SATB1 activates lineage-specifying genes (ThPOK, Runx3, CD4, CD8, Foxp3) by regulating their enhancers; SATB1-deficient thymocytes are misdirected into inappropriate T lineages and fail to generate NKT and Treg subsets. |
SATB1-deficient thymocyte analysis, ChIP/enhancer activity assays at lineage-specifying loci, flow cytometry lineage tracing |
Cell reports |
High |
28494867
|
| 2019 |
Loss of SATB1 in post-mitotic dopaminergic neurons activates a cellular senescence transcriptional program and SATB1 directly represses expression of the pro-senescence factor p21 in dopaminergic neurons. |
SATB1 knockout in human iPSC-derived dopaminergic neurons and in mice, ChIP for SATB1 at p21 locus, senescence marker analysis |
Cell stem cell |
High |
31543366
|
| 2019 |
Satb1 preferentially targets nucleosome-dense genomic regions; the homeodomain of Satb1 is dispensable for high-affinity binding but essential for binding specificity; Satb1-DNA interactions are mechanosensitive, with increased negative torsional stress enhancing Satb1 binding. Satb1 stabilizes base-unpairing regions (BURs) against melting. |
Single-molecule live-cell imaging, deep sequencing (SELEX/ChIP-seq), DNA torsional stress manipulation, homeodomain deletion mutants |
Nature communications |
High |
31324780
|
| 2019 |
SATB1 is required for secretory ameloblast cell polarity and directional amelogenin secretion; Satb1-null ameloblasts lose Tomes' processes, inter-ameloblastic adhesion, and apical F-actin architecture. SATB1 controls expression of Eps8 (an actin-regulator), and Eps8 loss at the apical surface underlies the polarity defect. |
Satb1-null mouse analysis, microarray for SATB1 targets, immunofluorescence for polarity markers and Eps8, amelogenin secretion assay |
BMC biology |
High |
31830989
|
| 2019 |
USP47 interacts with SATB1 and mediates its deubiquitination and stabilization; SMURF2 is an E3 ubiquitin ligase that promotes SATB1 degradation by increasing its ubiquitination; USP47 negatively regulates SMURF2, thereby controlling SATB1 protein levels and transcriptional activity. |
Co-immunoprecipitation, ubiquitination assays, USP47 knockdown/knockout, SMURF2 overexpression/knockdown, in vivo colon cancer model |
Cancer letters |
Medium |
30742943
|
| 2019 |
SATB1 directly represses SPARC expression in K562 cells by binding to a specific 17 bp DNA sequence in the third intron of the SPARC gene, as confirmed by ChIP with anti-SATB1 antibody; siRNA knockdown of SATB1 reduces SPARC expression. |
SATB1 overexpression, microarray, siRNA knockdown, ChIP with anti-SATB1, bioinformatics binding site identification |
Biochemical and biophysical research communications |
Medium |
17343824
|
| 2020 |
N6-methyladenine (N6-mA) DNA modification antagonizes SATB1 function: N6-mA deposited at SIDD (stress-induced DNA duplex destabilization) regions reduces SATB1-SIDD interactions by >500-fold in vitro, prevents SATB1 chromatin binding in vivo, and restricts euchromatin spread during trophoblast development. |
In vitro SATB1-DNA binding assay with N6-mA-modified substrates, ChIP for SATB1 in trophoblast stem cells with N6-mA manipulation, Hi-C chromatin domain analysis |
Nature |
High |
32669713
|
| 2021 |
Missense variants in the CUT1 and CUT2 DNA-binding domains of SATB1 result in stronger chromatin binding and increased transcriptional repression associated with severe neurodevelopmental phenotype; haploinsufficiency variants cause milder phenotype; premature truncation variants that escape NMD are transcriptionally active but mislocalized. |
Functional assays on 42 individuals with SATB1 variants, chromatin binding assays, transcriptional repression assays, localization studies |
American journal of human genetics |
High |
33513338
|
| 2022 |
SATB1 organizes T cell 3D genome architecture by constraining chromatin interactions around CTCF co-occupied sites; SATB1 depletion increases chromatin contacts among SATB1/CTCF co-occupied sites; SATB1 is required for retention of CTCF in the nuclear matrix but does not affect CTCF occupancy at chromatin. |
Hi-C, SATB1 depletion in human and murine T cells, ChIP-seq for CTCF, nuclear matrix fractionation |
Cell reports |
High |
37000624
|
| 2022 |
SATB1 shapes the 3D enhancer network of developing T cells: SATB1 is enriched at anchors of promoter-enhancer loops; SATB1 conditional KO reduces interactions among super-enhancers and between super-enhancers and promoters, impairing expression of master regulator genes including Bcl6 and the TCR locus. |
H3K27ac HiChIP, Hi-C, T cell-specific Satb1 conditional knockout, gene expression analysis |
Nature communications |
High |
36376298
|
| 2022 |
SATB1 controls DP thymocyte identity by globally regulating super-enhancer activity: in Satb1-deleted thymocytes, interactions among super-enhancers and between super-enhancers and promoters driving DP-specific genes are specifically decreased, redirecting cell identity. |
Single-cell RNA-seq, Hi-C, Satb1 conditional knockout in thymocytes, super-enhancer mapping |
Nature communications |
High |
36138028
|
| 2022 |
TGF-β-mediated repression of SATB1 promotes Tfh cell differentiation: Smad proteins downstream of TGF-β bind the Satb1 promoter to repress SATB1 expression, relieving SATB1-dependent repression of Icos and Pdcd1, which collectively drives Tfh differentiation and inhibits T follicular regulatory cell skewing. |
CD4-Cre Satb1 conditional knockout, TGF-β treatment of human T cells, Smad binding assay at Satb1 promoter, Icos/CXCL13 functional analysis |
Immunity |
High |
35021053
|
| 2005 |
During apoptosis, SATB1 undergoes caspase-3-mediated cleavage in Jurkat cells, forming a special 3D network distribution in early apoptosis before nuclear architecture collapse; cleavage is apoptosis-specific. |
Immunostaining, Western blot, caspase-3 inhibitor treatment, apoptosis induction in Jurkat cells |
Cell biology international |
Medium |
16377216
|
| 2017 |
SATB1 promotes Schwann cell viability and migration by binding the SHIP1 gene promoter region and recruiting HDAC1 to repress SHIP1 expression, thereby activating the PI3K/AKT signaling pathway. |
ChIP assay for SATB1 at SHIP1 promoter, HDAC1 co-IP, Satb1 knockout/overexpression, SHIP1 rescue experiment, PI3K/AKT pathway analysis |
European review for medical and pharmacological sciences |
Medium |
30024617
|
| 2024 |
SATB1, miR-22-3p, and GBA form a single regulatory pathway in dopaminergic neurons: SATB1 transcriptionally represses MIR22HG; loss of SATB1 derepresses miR-22-3p, which reduces GBA expression, causing glucocerebroside accumulation that impairs lysosomal and mitochondrial function and induces cellular senescence. |
Human and murine neuronal lines, iPSC-derived dopaminergic neurons, mouse models; SATB1 KO/overexpression, miR-22-3p manipulation, GBA activity assays, senescence markers |
Aging cell |
High |
38303548
|