Affinage

SATB1

DNA-binding protein SATB1 · UniProt Q01826

Length
763 aa
Mass
86.0 kDa
Annotated
2026-06-10
100 papers in source corpus 35 papers cited in narrative 35 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SATB1 is a nuclear genome organizer and transcription factor that binds matrix attachment regions (MARs) in the DNA minor groove via a novel bipartite DNA-binding domain requiring both N- and C-terminal ends for full activity, making virtually no contact with the bases (PMID:8114718). It preferentially targets nucleosome-dense base-unpairing regions (BURs), stabilizes them against melting, binds in a mechanosensitive manner enhanced by negative torsional stress, and uses its homeodomain for binding specificity rather than affinity (PMID:31324780). By tethering its bound sites to the nuclear matrix, an activity required for transcriptional repression, SATB1 folds large chromatin domains into loops that coordinate gene clusters (PMID:15851481, PMID:17057718). In T cells it functions as a global orchestrator of development, looping the 200-kb TH2 cytokine locus and recruiting transcription factors and RNA polymerase II to drive cytokine expression (PMID:10716941, PMID:17057718), and it organizes 3D genome architecture by constraining chromatin interactions around CTCF co-occupied sites and shaping super-enhancer/promoter loop networks that specify Treg, DP thymocyte, and lineage identity (PMID:27992401, PMID:37000624, PMID:36376298, PMID:36138028). SATB1 output is set by its post-translational state and partners: it recruits corepressor machinery (CtBP1, HDAC1, NuRD) through defined motifs, with PKC phosphorylation at S185 promoting repression and acetylation disrupting CtBP1 binding to switch toward activation (PMID:19103759, PMID:20694677, PMID:28099864), while β-catenin/p300 recruitment supports activation (PMID:20126258). Its abundance and activity are tuned by sumoylation at K744 (PMID:18408014), a USP47/SMURF2 ubiquitination axis (PMID:30742943), and by N6-methyladenine DNA modification at SIDD sequences that antagonizes chromatin binding (PMID:32669713). In neurons SATB1 regulates immediate-early gene timing and dendritic architecture (PMID:22064485), and represses the pro-senescence factor p21 and a MIR22HG/miR-22-3p/GBA pathway in dopaminergic neurons (PMID:31543366, PMID:38303548). Missense variants in its CUT1/CUT2 DNA-binding domains cause a severe neurodevelopmental disorder through gain of chromatin binding and repression, while haploinsufficiency yields a milder phenotype (PMID:33513338).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1994 High

    Established the molecular basis of SATB1-DNA recognition, showing it reads DNA structure rather than sequence through a novel bipartite binding domain.

    Evidence Deletion mutagenesis and in vitro DNA-binding assays on cloned mouse SATB1

    PMID:8114718

    Open questions at the time
    • No structure of the bipartite domain bound to DNA
    • Did not address in vivo chromatin targets
  2. 1999 High

    Showed SATB1 DNA binding can be antagonized by a protein partner, introducing the concept of regulated occupancy at MARs.

    Evidence Reciprocal co-IP, GST pulldown, far-Western, and reporter assays for SATB1-CDP interaction in T cells

    PMID:10373541

    Open questions at the time
    • Physiological contexts where CDP antagonism operates not defined
    • Stoichiometry of competition unknown
  3. 2000 High

    Defined SATB1 as a global, in vivo orchestrator of temporal and spatial gene expression rather than a single-locus factor.

    Evidence SATB1-null mouse with flow cytometry and 589-gene expression profiling of T-cell development

    PMID:10716941

    Open questions at the time
    • Direct vs indirect targets not separated
    • Mechanism linking binding to gene deregulation not resolved here
  4. 2005 High

    Separated nuclear matrix tethering from DNA binding, establishing matrix anchoring as the functional requirement for SATB1-mediated repression.

    Evidence NMTS deletion constructs with nuclear fractionation, GFP localization, and retroviral MMTV reporter assays

    PMID:15851481

    Open questions at the time
    • Matrix protein partners of the NMTS unidentified
    • Single lab, single reporter system
  5. 2006 High

    Demonstrated that SATB1 physically loops a large gene cluster into transcriptionally competent chromatin, providing the paradigm for its genome-folding function.

    Evidence RNAi knockdown, chromosome conformation/looping assays, and ChIP at the TH2 cytokine locus

    PMID:17057718

    Open questions at the time
    • How looping mechanically follows from matrix anchoring not resolved
    • Order of recruitment of co-factors undefined
  6. 2008 High

    Identified post-translational switches controlling SATB1 output: corepressor recruitment via a PVPLS motif and its reversal by acetylation, plus sumoylation directing SATB1 to PML bodies.

    Evidence Co-IP, motif mutagenesis, ChIP, and gene profiling for CtBP1; yeast two-hybrid, K744R mutagenesis and SUMO-fusion rescue for sumoylation

    PMID:18408014 PMID:19103759

    Open questions at the time
    • Acetyltransferase/deacetylase enzymes for the activation switch not fully defined
    • Functional consequence of PML targeting beyond caspase cleavage unclear
  7. 2009 High

    Extended SATB1 function to large-scale silencing and stem-cell fate, showing it is required for Xist-mediated silencing and regulates pluripotency loci.

    Evidence Loss- and gain-of-function in lymphoma and fibroblast models with Xist FISH; Satb1-null ES cells with ChIP at the Nanog locus and Satb2 epistasis

    PMID:19386260 PMID:19933152

    Open questions at the time
    • Mechanistic link between SATB1 and Xist silencing machinery unresolved
    • Basis of opposing SATB1/SATB2 effects at shared loci not defined
  8. 2010 Medium

    Connected SATB1 to upstream signaling, with PKC phosphorylation enhancing repression and Wnt/β-catenin recruitment promoting activation and TH2 commitment.

    Evidence In vitro/in vivo kinase and reporter assays for S185; co-IP, ChIP, and Wnt-inhibitor/knockdown experiments for β-catenin/p300

    PMID:20126258 PMID:20694677

    Open questions at the time
    • S185 finding from a methods chapter with limited primary data
    • Integration of phosphorylation and acetylation switches not jointly tested
  9. 2011 High

    Established direct SATB1 control of neuronal gene programs and morphology, broadening its role beyond the immune system.

    Evidence ChIP at immediate-early gene loci and dendritic spine quantification in Satb1-null cortical neurons

    PMID:22064485

    Open questions at the time
    • How SATB1 sets IEG timing mechanistically unknown
    • Cofactors in neurons not identified
  10. 2013 High

    Showed SATB1 directs hematopoietic lineage choice and links its decline to aging-associated loss of lymphopoietic potential.

    Evidence Knockout, transplantation rescue, and retroviral overexpression in HSCs and ES cells with gene profiling

    PMID:23791645

    Open questions at the time
    • Direct target genes mediating lymphoid bias not pinpointed
    • Cause of Satb1 decline in aged HSCs unknown
  11. 2013 Medium

    Demonstrated direct, p53-independent transcriptional repression of p21 by SATB1, coupling it to cell-cycle and apoptosis control in malignancy.

    Evidence ChIP, luciferase and promoter mutational analysis with siRNA and cell-cycle readouts in lymphoma cells; gain-of-function FasL activation in Sezary cells

    PMID:21270445 PMID:24747435

    Open questions at the time
    • Cofactors at the p21 promoter not defined
    • FasL regulation shown in a single lymphoma model
  12. 2015 High

    Defined SATB1-driven transcriptional programs in neural differentiation and circuit assembly, including a HuD-SATB1 feedback loop and adhesion-molecule control of dendrite targeting.

    Evidence mRNA stability/promoter assays for HuD-SATB1-NeuroD1; Cntn5 conditional KO and electrophysiology in retinal ooDSGCs; ChIP/conditional KO for Notch1 in DCs

    PMID:26305964 PMID:26876172 PMID:28781169

    Open questions at the time
    • Direct vs indirect target distinction incomplete for some loci
    • HuD feedback loop from single lab
  13. 2016 High

    Established SATB1 as an activator of cell-type-specific super-enhancers, mechanistically linking it to Treg and thymocyte lineage identity and tolerance.

    Evidence T-cell-specific conditional KO with H3K27ac ChIP-seq super-enhancer mapping and autoimmunity phenotyping; enhancer/lineage analysis in post-selection thymocytes

    PMID:27992401 PMID:28494867

    Open questions at the time
    • How SATB1 selects which enhancers to activate vs repress unresolved
    • Direct enhancer-binding stoichiometry not quantified
  14. 2017 High

    Identified SATB1-NuRD recruitment as the repressive mechanism keeping PD-1 silenced, and revealed TGF-β/Smad suppression of SATB1 as an immune-evasion axis.

    Evidence ChIP for NuRD at Pdcd1, Smad-binding/competition assays, and Satb1-deficient T cells with 40-fold PD-1 increase

    PMID:28099864

    Open questions at the time
    • Structural basis of Smad-SATB1 competition unknown
    • Generality across other immune checkpoints untested
  15. 2019 High

    Resolved the biophysics of SATB1 chromatin targeting and the mechanisms tuning its protein level and DNA access.

    Evidence Single-molecule imaging and deep sequencing of BUR binding; USP47/SMURF2 ubiquitination assays; in vitro and in vivo N6-mA antagonism with Hi-C; ChIP-based repression of SPARC

    PMID:17343824 PMID:30742943 PMID:31324780 PMID:32669713

    Open questions at the time
    • Enzymes writing N6-mA at SIDD in mammals not fully defined
    • USP47/SMURF2 axis from single lab
  16. 2019 High

    Extended SATB1 to non-immune cellular architecture and to neuronal aging, repressing p21 to prevent dopaminergic-neuron senescence and controlling epithelial polarity via Eps8.

    Evidence ChIP at p21 in iPSC-derived neurons and mice; microarray and immunofluorescence in Satb1-null ameloblasts; ChIP/HDAC1 recruitment at SHIP1 in Schwann cells

    PMID:30024617 PMID:31543366 PMID:31830989

    Open questions at the time
    • Mechanism linking p21 repression to senescence program incomplete
    • Schwann cell SHIP1 finding from a single lower-tier study
  17. 2021 High

    Linked SATB1 dysfunction causally to human neurodevelopmental disease and mapped variant class to molecular consequence.

    Evidence Functional chromatin-binding, repression, and localization assays across variants in 42 individuals

    PMID:33513338

    Open questions at the time
    • How gain-of-binding variants produce neurodevelopmental pathology at the circuit level unknown
    • Tissue-specific consequences not modeled
  18. 2022 High

    Defined SATB1 as a constraint on 3D genome architecture acting through CTCF co-occupied sites and super-enhancer loop networks to enforce developmental identity.

    Evidence Hi-C, HiChIP, ChIP-seq, scRNA-seq, and nuclear matrix fractionation in human and murine T cells and conditional KO thymocytes; Smad-Satb1 promoter axis driving Tfh differentiation

    PMID:35021053 PMID:36138028 PMID:36376298 PMID:37000624

    Open questions at the time
    • Whether SATB1 constrains vs facilitates contacts is context-dependent and mechanism unresolved
    • Direct molecular link between SATB1 and CTCF matrix retention unknown
  19. 2024 High

    Assembled a complete SATB1 regulatory pathway in dopaminergic neurons connecting transcriptional repression to lysosomal/mitochondrial dysfunction and senescence.

    Evidence Stepwise KO/overexpression at SATB1, miR-22-3p, and GBA nodes with activity and senescence readouts across multiple model systems

    PMID:38303548

    Open questions at the time
    • Relative contribution of the p21 and GBA arms to senescence not weighted
    • Relevance to human Parkinsonian pathology not directly tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SATB1 mechanically converts matrix anchoring and BUR binding into specific loop formation, and what determines its context-dependent switch between repression and activation genome-wide, remain unresolved.
  • No structural model of SATB1 organizing a chromatin loop
  • Rules governing repressor vs activator complex recruitment at each site not defined
  • Integration of phosphorylation, acetylation, sumoylation, and ubiquitination into a single regulatory logic untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0003677 DNA binding 3 GO:0060090 molecular adaptor activity 3 GO:0003723 RNA binding 1
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 3
Pathway
R-HSA-168256 Immune System 5 R-HSA-4839726 Chromatin organization 5 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-1266738 Developmental Biology 4 R-HSA-8953897 Cellular responses to stimuli 2
Complex memberships
CtBP1/HDAC1 corepressor complexNuRD complex (SATB1-recruited)

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
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

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 SATB1 packages densely looped, transcriptionally active chromatin for coordinated expression of cytokine genes. Nature genetics 461 17057718
2000 The MAR-binding protein SATB1 orchestrates temporal and spatial expression of multiple genes during T-cell development. Genes & development 308 10716941
2016 Guidance of regulatory T cell development by Satb1-dependent super-enhancer establishment. Nature immunology 297 27992401
2010 Global regulator SATB1 recruits beta-catenin and regulates T(H)2 differentiation in Wnt-dependent manner. PLoS biology 170 20126258
2019 Loss of SATB1 Induces p21-Dependent Cellular Senescence in Post-mitotic Dopaminergic Neurons. Cell stem cell 159 31543366
2009 SATB1 defines the developmental context for gene silencing by Xist in lymphoma and embryonic cells. Developmental cell 156 19386260
2022 TGF-β-mediated silencing of genomic organizer SATB1 promotes Tfh cell differentiation and formation of intra-tumoral tertiary lymphoid structures. Immunity 153 35021053
2007 The third dimension of gene regulation: organization of dynamic chromatin loopscape by SATB1. Current opinion in genetics & development 143 17913490
2017 SATB1 Expression Governs Epigenetic Repression of PD-1 in Tumor-Reactive T Cells. Immunity 136 28099864
2009 Satb1 and Satb2 regulate embryonic stem cell differentiation and Nanog expression. Genes & development 116 19933152
2012 Genome organizing function of SATB1 in tumor progression. Seminars in cancer biology 102 22771615
1994 A novel DNA-binding motif in the nuclear matrix attachment DNA-binding protein SATB1. Molecular and cellular biology 101 8114718
2009 The mRNA expression of SATB1 and SATB2 in human breast cancer. Cancer cell international 94 19642980
2021 A microRNA-21-mediated SATB1/S100A9/NF-κB axis promotes chronic obstructive pulmonary disease pathogenesis. Science translational medicine 92 34818056
2017 Satb1 Regulates Contactin 5 to Pattern Dendrites of a Mammalian Retinal Ganglion Cell. Neuron 91 28781169
2016 Satb1 Overexpression Drives Tumor-Promoting Activities in Cancer-Associated Dendritic Cells. Cell reports 90 26876172
2013 The Satb1 protein directs hematopoietic stem cell differentiation toward lymphoid lineages. Immunity 90 23791645
2012 Upregulation of SATB1 promotes tumor growth and metastasis in liver cancer. Liver international : official journal of the International Association for the Study of the Liver 90 22583549
2010 Expression of SATB1 and heparanase in gastric cancer and its relationship to clinicopathologic features. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 85 20955458
2017 Essential Roles of SATB1 in Specifying T Lymphocyte Subsets. Cell reports 83 28494867
2015 Wnt/β-catenin signaling regulated SATB1 promotes colorectal cancer tumorigenesis and progression. Oncogene 75 26165840
2019 Reversible regulation of SATB1 ubiquitination by USP47 and SMURF2 mediates colon cancer cell proliferation and tumor progression. Cancer letters 74 30742943
2011 Satb1 ablation alters temporal expression of immediate early genes and reduces dendritic spine density during postnatal brain development. Molecular and cellular biology 72 22064485
2010 SATB1 dictates expression of multiple genes including IL-5 involved in human T helper cell differentiation. Blood 66 20522714
2020 N6-methyladenine in DNA antagonizes SATB1 in early development. Nature 59 32669713
2011 Deficiency of SATB1 expression in Sezary cells causes apoptosis resistance by regulating FasL/CD95L transcription. Blood 59 21270445
2008 Acetylation-dependent interaction of SATB1 and CtBP1 mediates transcriptional repression by SATB1. Molecular and cellular biology 59 19103759
2015 SATB1 Plays a Critical Role in Establishment of Immune Tolerance. Journal of immunology (Baltimore, Md. : 1950) 55 26667169
2012 MicroRNA-191 triggers keratinocytes senescence by SATB1 and CDK6 downregulation. Biochemical and biophysical research communications 53 22683624
2012 Upregulation of SATB1 is associated with the development and progression of glioma. Journal of translational medicine 51 22839214
2015 Positive feedback between RNA-binding protein HuD and transcription factor SATB1 promotes neurogenesis. Proceedings of the National Academy of Sciences of the United States of America 50 26305964
2005 Nuclear matrix binding regulates SATB1-mediated transcriptional repression. The Journal of biological chemistry 49 15851481
2014 Expression of SATB1 promotes the growth and metastasis of colorectal cancer. PloS one 45 24971456
2013 SATB1 expression is associated with biologic behavior in colorectal carcinoma in vitro and in vivo. PloS one 45 23326301
2019 Satb1 regulates the effector program of encephalitogenic tissue Th17 cells in chronic inflammation. Nature communications 44 30710091
1999 Homeoproteins CDP and SATB1 interact: potential for tissue-specific regulation. Molecular and cellular biology 44 10373541
2019 The Role of SATB1 in Tumour Progression and Metastasis. International journal of molecular sciences 42 31450715
2008 SUMO conjugation to the matrix attachment region-binding protein, special AT-rich sequence-binding protein-1 (SATB1), targets SATB1 to promyelocytic nuclear bodies where it undergoes caspase cleavage. The Journal of biological chemistry 42 18408014
2018 SATB1 in Malignant T Cells. The Journal of investigative dermatology 41 29751003
2021 Mutation-specific pathophysiological mechanisms define different neurodevelopmental disorders associated with SATB1 dysfunction. American journal of human genetics 40 33513338
2016 Epigenetic regulation of long noncoding RNA UCA1 by SATB1 in breast cancer. BMB reports 40 27697109
2015 miR-23a suppresses proliferation of osteosarcoma cells by targeting SATB1. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 40 25619478
2015 SATB1 overexpression regulates the development and progression in bladder cancer through EMT. PloS one 40 25706386
2014 SATB1 and 2 in colorectal cancer. Carcinogenesis 40 25543122
2018 Functional relevance of SATB1 in immune regulation and tumorigenesis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 39 29772444
2018 miR-7-5p inhibits cell migration and invasion in glioblastoma through targeting SATB1. Oncology letters 38 30675243
2022 SATB1/SLC7A11/HO-1 Axis Ameliorates Ferroptosis in Neuron Cells After Ischemic Stroke by Danhong Injection. Molecular neurobiology 36 36274077
2013 Silencing SATB1 with siRNA inhibits the proliferation and invasion of small cell lung cancer cells. Cancer cell international 36 23379909
2012 SATB1-mediated functional packaging of chromatin into loops. Methods (San Diego, Calif.) 36 22782115
2013 Expression and biological roles of SATB1 in human bladder cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 34 23696028
2016 SATB1 and SATB2 play opposing roles in c-Myc expression and progression of colorectal cancer. Oncotarget 33 26701851
2014 SATB1 overexpression promotes malignant T-cell proliferation in cutaneous CD30+ lymphoproliferative disease by repressing p21. Blood 33 24747435
2013 FoxP3, Helios, and SATB1: roles and relationships in regulatory T cells. International immunopharmacology 33 23428911
2022 The 3D enhancer network of the developing T cell genome is shaped by SATB1. Nature communications 32 36376298
2012 Chromatin organizer SATB1 as a novel molecular target for cancer therapy. Current drug targets 32 22998183
2019 Satb1 integrates DNA binding site geometry and torsional stress to differentially target nucleosome-dense regions. Nature communications 31 31324780
2019 SATB1 establishes ameloblast cell polarity and regulates directional amelogenin secretion for enamel formation. BMC biology 28 31830989
2022 Chromatin organizer SATB1 controls the cell identity of CD4+ CD8+ double-positive thymocytes by regulating the activity of super-enhancers. Nature communications 27 36138028
2013 Plakoglobin represses SATB1 expression and decreases in vitro proliferation, migration and invasion. PloS one 27 24260116
2019 Unraveling the role of H3K4 trimethylation and lncRNA HOTAIR in SATB1 and DUSP4-dependent survival of virulent Mycobacterium tuberculosis in macrophages. Tuberculosis (Edinburgh, Scotland) 26 32090865
2018 Variable SATB1 Levels Regulate Hematopoietic Stem Cell Heterogeneity with Distinct Lineage Fate. Cell reports 25 29898394
2024 The SATB1-MIR22-GBA axis mediates glucocerebroside accumulation inducing a cellular senescence-like phenotype in dopaminergic neurons. Aging cell 24 38303548
2019 MiR-191-5p inhibits lung adenocarcinoma by repressing SATB1 to inhibit Wnt pathway. Molecular genetics & genomic medicine 24 31724324
2019 Hepatitis B Virus X Protein Induces SATB1 Expression Through Activation of ERK and p38MAPK Pathways to Suppress Anoikis. Digestive diseases and sciences 23 31147803
2018 The Special AT-rich Sequence Binding Protein 1 (SATB1) and its role in solid tumors. Cancer letters 23 29306014
2016 SATB1 promotes prostate cancer metastasis by the regulation of epithelial-mesenchymal transition. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 23 27044805
2016 SATB1 is Correlated with Progression and Metastasis of Breast Cancers: A Meta-Analysis. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 23 27161300
2016 Regulation of SATB1 during thymocyte development by TCR signaling. Molecular immunology 23 27454343
2020 SATB1-mediated chromatin landscape in T cells. Nucleus (Austin, Tex.) 22 33356851
2017 SATB1 promotes epithelial-mesenchymal transition and metastasis in prostate cancer. Oncology letters 22 28454436
2015 Divergent expression patterns of SATB1 mRNA and SATB1 protein in colorectal cancer and normal tissues. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 22 25874491
2012 Satb1 and Satb2 are dispensable for X chromosome inactivation in mice. Developmental cell 22 23079603
2019 MiR-122-5p suppresses cell proliferation, migration and invasion by targeting SATB1 in nasopharyngeal carcinoma. European review for medical and pharmacological sciences 21 30720170
2015 Expression of SATB1 and HER2 in breast cancer and the correlations with clinicopathologic characteristics. Diagnostic pathology 21 25956130
2023 SATB1 regulates 3D genome architecture in T cells by constraining chromatin interactions surrounding CTCF-binding sites. Cell reports 20 37000624
2021 Role of Satb1 and Satb2 Transcription Factors in the Glutamate Receptors Expression and Ca2+ Signaling in the Cortical Neurons In Vitro. International journal of molecular sciences 20 34073140
2017 Expression and clinical significance of SATB1 and TLR4 in breast cancer. Oncology letters 20 28927120
2015 Oncolytic virus carrying shRNA targeting SATB1 inhibits prostate cancer growth and metastasis. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 20 26084613
2022 Expression of Circ_Satb1 Is Decreased in Mesial Temporal Lobe Epilepsy and Regulates Dendritic Spine Morphology. Frontiers in molecular neuroscience 19 35310884
2018 Satb1 promotes Schwann cell viability and migration via activation of PI3K/AKT pathway. European review for medical and pharmacological sciences 19 30024617
2017 Satb1: Restraining PD1 and T Cell Exhaustion. Immunity 19 28099863
2016 SATB1 expression is correlated with β-catenin associated epithelial-mesenchymal transition in colorectal cancer. Cancer biology & therapy 19 26810818
2019 Divergent SATB1 expression across human life span and tissue compartments. Immunology and cell biology 18 30803026
2015 SATB1 Promotes Pancreatic Cancer Growth and Invasion Depending on MYC Activation. Digestive diseases and sciences 18 26108419
2012 ATM suppresses SATB1-induced malignant progression in breast epithelial cells. PloS one 18 23251624
2021 SATB1 Knockdown Inhibits Proliferation and Invasion and Decreases Chemoradiation Resistance in Nasopharyngeal Carcinoma Cells by Reversing EMT and Suppressing MMP-9. International journal of medical sciences 17 33390772
2013 Silencing SATB1 inhibits proliferation of human osteosarcoma U2OS cells. Molecular and cellular biochemistry 17 23516037
2012 Correlation between SATB1 and Bcl-2 expression in human glioblastoma multiforme. Molecular medicine reports 17 23076250
2005 The behavior of SATB1, a MAR-binding protein, in response to apoptosis stimulation. Cell biology international 17 16377216
2017 The chromatin modifier Satb1 regulates cell fate through Fgf signalling in the early mouse embryo. Development (Cambridge, England) 16 28289135
2016 Expression of SATB1 and HER2 in gastric cancer and its clinical significance. European review for medical and pharmacological sciences 16 27338049
2013 SATB1 collaborates with loss of p16 in cellular transformation. Oncogene 16 23686316
2019 NF-κB Signaling and IL-4 Signaling Regulate SATB1 Expression via Alternative Promoter Usage During Th2 Differentiation. Frontiers in immunology 15 31001272
2017 Analysis of cellular and molecular antitumor effects upon inhibition of SATB1 in glioblastoma cells. BMC cancer 15 28049521
2015 Expression and significance of SATB1 in the development of breast cancer. Genetics and molecular research : GMR 15 25966097
2010 Phosphorylation-dependent regulation of SATB1, the higher-order chromatin organizer and global gene regulator. Methods in molecular biology (Clifton, N.J.) 15 20694677
2007 SATB1 regulates SPARC expression in K562 cell line through binding to a specific sequence in the third intron. Biochemical and biophysical research communications 15 17343824
2018 The role of SATB1 in HTR8/SVneo cells and pathological mechanism of preeclampsia. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 14 29307244
2016 Hepatic SATB1 induces paracrine activation of hepatic stellate cells and is upregulated by HBx. Scientific reports 14 27883059
2014 Fluorosed mouse ameloblasts have increased SATB1 retention and Gαq activity. PloS one 14 25090413

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