Affinage

SP3

Transcription factor Sp3 · UniProt Q02447

Length
781 aa
Mass
81.9 kDa
Annotated
2026-04-28
100 papers in source corpus 28 papers cited in narrative 29 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SP3 is a ubiquitously expressed zinc-finger transcription factor that binds GC-box elements genome-wide, functioning as both an activator and a repressor of transcription depending on isoform, promoter context, and post-translational modification state. SP3 competes with SP1 for shared GC-box sites, and its shorter internally initiated isoforms lack activation capacity, serving as potent transcriptional repressors (PMID:8070411, PMID:9224612, PMID:25793500). SUMO conjugation at K551, mediated by the E3 ligase PIAS1, converts SP3 into a silencer that recruits heterochromatin factors including SETDB1, SUV4-20H, HP1, and Mi-2, leading to H3K9 and H4K20 trimethylation, while acetylation by p300 and calpain-mediated cleavage provide additional regulatory inputs (PMID:12419227, PMID:12356736, PMID:18617891, PMID:17316402). SP3 is essential in vivo for tooth development, ossification, hematopoiesis, cardiac morphogenesis, and proplatelet formation, demonstrating non-redundant functions distinct from SP1 (PMID:10675334, PMID:11472836, PMID:12676787, PMID:17923686, PMID:25538045).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1994 High

    Establishing that SP3 is not simply redundant with SP1 but acts as a GC-box competitor that represses SP1-mediated activation, answering the fundamental question of why two factors with identical DNA-binding specificity coexist.

    Evidence Co-transfection in mammalian and Drosophila SL2 cells with deletion and chimeric mutants of SP3

    PMID:8070411

    Open questions at the time
    • Mechanism of repression beyond site competition was unknown
    • Whether SP3 could activate transcription in any context remained open
    • In vivo relevance of competition not tested
  2. 1997 High

    Discovery that the SP3 gene produces multiple isoforms via internal translational initiation resolved why SP3 behaves as a repressor in most contexts — the shorter isoforms lack activation domains and act as dominant repressors.

    Evidence In vitro translation, mutagenesis of internal start sites, reporter assays

    PMID:9224612

    Open questions at the time
    • Post-translational modifications of individual isoforms not characterized
    • Relative abundance of isoforms in different tissues unknown
  3. 2000 High

    Knockout of SP3 in mice revealed essential, non-redundant in vivo roles in tooth development and surfactant production, establishing that SP3 loss is not compensated by SP1.

    Evidence Homologous recombination gene knockout in mice with histological and gene expression analysis

    PMID:10675334

    Open questions at the time
    • Molecular targets in ameloblasts not identified
    • Cause of respiratory failure not fully dissected
    • Conditional tissue-specific requirements not tested
  4. 2001 High

    Two parallel discoveries — that SP3 is regulated by acetylation at a critical lysine and that SP3 is required for skeletal ossification — expanded the picture of SP3 as a post-translationally regulated factor with broad developmental functions.

    Evidence In vitro transcription with SP1/SP3-depleted nuclear extract and acetylation mutagenesis (PMID:11812829); SP3 knockout mouse skeletal analysis and ES cell osteogenic differentiation (PMID:11472836)

    PMID:11472836 PMID:11812829

    Open questions at the time
    • Identity of the acetyltransferase responsible in vivo not determined at this stage
    • Relationship between acetylation and sumoylation at the same or nearby lysines unclear
  5. 2002 High

    The discovery that SUMO modification at K551, catalyzed by E3 ligase PIAS1, switches SP3 from activator to repressor and relocalizes it to nuclear bodies provided the central post-translational mechanism controlling SP3 activity.

    Evidence SUMO acceptor lysine mutagenesis, SUMO-1 gene fusions, immunofluorescence, in vitro/in vivo SUMO conjugation assays with PIAS1

    PMID:12356736 PMID:12419227

    Open questions at the time
    • How SUMO-SP3 recruits silencing machinery not yet established
    • Regulation of PIAS1-mediated sumoylation in physiological contexts unknown
    • Whether desumoylation is signal-regulated not addressed
  6. 2002 High

    Identification of SP3 in a distinct nuclear complex with CK2-phosphorylated HDAC2, separate from SP1 complexes, established that SP3 mediates transcriptional repression through histone deacetylase recruitment.

    Evidence Reciprocal co-immunoprecipitation, in vitro kinase assay, alkaline phosphatase treatment in breast cancer cells

    PMID:12176973

    Open questions at the time
    • Genomic targets of the SP3-HDAC2 complex not mapped
    • Whether SUMO modification of SP3 is required for HDAC2 interaction not tested
  7. 2003 High

    Demonstration of cell-autonomous hematopoietic defects in SP3-null mice — including arrested T-cell development, reduced B cells, and impaired erythropoiesis — broadened SP3's essential developmental roles to the blood system.

    Evidence SP3 knockout mice with bone marrow transplantation proving cell-autonomous defects, in vitro differentiation assays

    PMID:12676787

    Open questions at the time
    • Direct transcriptional targets in hematopoietic progenitors not identified
    • Relative contribution of SP3 isoforms to hematopoiesis unknown
  8. 2005 High

    High-resolution imaging and re-ChIP studies revealed that SP1 and SP3 occupy distinct non-overlapping nuclear domains and do not co-occupy the same promoter molecule simultaneously, reframing the competition model as one of mutually exclusive occupancy.

    Evidence Deconvolution microscopy, nuclear matrix fractionation, ChIP/re-ChIP at trefoil factor 1 promoter

    PMID:15987735

    Open questions at the time
    • Whether mutual exclusivity applies genome-wide or only at select loci not determined
    • Dynamic exchange rates between SP1 and SP3 at promoters not measured
  9. 2007 High

    SP3 was shown to be essential for cardiac morphogenesis, with direct ChIP evidence of SP3 binding to the Carp promoter in vivo, linking SP3 loss to defective heart looping and structural malformations.

    Evidence SP3 knockout mice on C57BL/6 background, ChIP of Carp promoter, microarray analysis of E10.5 hearts

    PMID:17923686

    Open questions at the time
    • Full set of direct cardiac target genes not delineated
    • Whether cardiac defect is SP3-isoform specific not tested
  10. 2008 High

    The mechanistic link between SUMO-SP3 and heterochromatin was completed by showing that DNA-bound sumoylated SP3 recruits Mi-2, MBT-domain proteins, HP1, SETDB1, and SUV4-20H to trigger H3K9me3 and H4K20me3, explaining how a single transcription factor nucleates stable gene silencing.

    Evidence ChIP for multiple histone marks and co-repressor proteins using sumoylation-competent and -deficient SP3 constructs

    PMID:18617891

    Open questions at the time
    • Whether this heterochromatin mechanism operates at endogenous SP3 target genes genome-wide unknown
    • Structural basis for SUMO-dependent co-repressor recruitment not resolved
  11. 2015 High

    Genome-wide ChIP-seq confirmed that SP1 and SP3 occupy essentially identical GC-box promoter sites, and that the zinc-finger domain alone dictates SP3 binding-site selection, resolving the question of genomic target overlap at a global scale.

    Evidence ChIP-seq in wild-type and SP3 knockout MEFs with zinc-finger deletion mutant re-expression

    PMID:25793500

    Open questions at the time
    • What determines differential functional outcomes (activation vs. repression) at shared sites not explained by binding alone
    • Contribution of non-DNA-binding cofactor interactions to target gene selectivity unclear
  12. 2017 High

    SP3 was shown to facilitate HDAC2 recruitment specifically to synaptic plasticity gene promoters in neurons, with SP3 knockdown phenocopying HDAC2 loss, establishing a neuronal gene-regulatory function for the SP3-HDAC2 axis.

    Evidence RNAi knockdown, ChIP-seq, and HDAC2 fragment rescue in a neurodegeneration mouse model

    PMID:28793257

    Open questions at the time
    • Whether SP3 sumoylation is required for HDAC2 recruitment to synaptic genes not tested
    • Which SP3 isoforms operate in mature neurons not determined
  13. 2019 High

    Single-cell and ChIP-seq analyses in hematopoietic progenitors showed that SP3 cooperates with SP1 but cannot substitute for SP1's DNA-binding function, establishing a model of obligate SP1-SP3 partnership rather than simple redundancy in hematopoiesis.

    Evidence ChIP-seq in hematopoietic progenitors, genetic complementation with SP1 DNA-binding-domain mutant, single-cell gene expression profiling

    PMID:31164147

    Open questions at the time
    • Biochemical nature of SP1-SP3 functional cooperation at shared sites not defined
    • Whether SP3-specific cofactors contribute to non-redundant hematopoietic functions unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how cells regulate the switch between activating and repressive SP3 states at specific genomic loci, including the signaling pathways that control the balance of SP3 sumoylation, acetylation, and isoform expression in different developmental and physiological contexts.
  • No structural model of SP3 or its SUMO-modified form exists
  • Genome-wide mapping of SUMO-SP3 versus unmodified SP3 occupancy has not been performed
  • The interplay between SP3 acetylation and sumoylation at the same critical lysine region is not resolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003677 DNA binding 4
Localization
GO:0005634 nucleus 2 GO:0005654 nucleoplasm 1
Pathway
R-HSA-74160 Gene expression (Transcription) 6 R-HSA-1266738 Developmental Biology 5 R-HSA-168256 Immune System 2 R-HSA-4839726 Chromatin organization 1
Partners
EP300GABPAHDAC2MYCPIAS1RELASP1UBE2I
Complex memberships
SP3-HDAC2-CK2 complexSUMO-SP3/SETDB1/HP1/Mi-2 silencing complex

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 Sp3 represses Sp1-mediated transcriptional activation by competing with Sp1 for shared GC-box binding sites; a DNA-binding domain deletion mutant of Sp3 fails to inhibit Sp1, confirming competition-based mechanism. Sp3 cannot activate transcription in Drosophila SL2 cells lacking endogenous Sp factors, and chimeric domain-swap experiments show that Sp3 glutamine-rich and D domains cannot functionally replace Sp1 counterparts. Co-transfection in mammalian cells and Drosophila SL2 cells, deletion/chimeric mutant analysis, antibody generation The EMBO journal High 8070411
1997 The Sp3 gene encodes multiple protein isoforms via internal translational initiation within the trans-activation domain; internally initiated Sp3 proteins (80 kDa) bind GC boxes but lack transcriptional activation capacity and instead function as potent repressors of Sp1/Sp3-mediated transcription. In vitro translation, transfection of reporter constructs, immunoblotting, mutational mapping of internal start sites Nucleic acids research High 9224612
2002 Sp3 is sumoylated at a single lysine residue (K551) in vivo and in vitro; SUMO modification represses Sp3 transcriptional activity and relocalizes it to the nuclear periphery and nuclear dots. The SUMO-1 protease SuPr-1 or mutation of acceptor lysines converts Sp3 to a strong activator with diffuse nuclear localization. Covalent SUMO-1 fusion to Sp3 is sufficient to recapitulate repression and relocalization. SUMO acceptor lysine mutagenesis, SUMO-1 protease expression, SUMO-1 gene fusion, indirect immunofluorescence, transcription reporter assays Molecular cell High 12419227
2002 PIAS1 acts as an E3 SUMO ligase for Sp3, stimulating SUMO conjugation at lysine within the IKXE motif located between the second glutamine-rich activation domain and the DNA-binding domain. SUMO-modified Sp3 binds DNA with similar specificity/affinity as unmodified Sp3, but DNA-bound Sp3 does not serve as a substrate for SUMO modification. In vivo and in vitro SUMO conjugation assays, mutational analysis of IKXE motif, co-immunoprecipitation of PIAS1 with Sp3 and Ubc9, transcriptional reporter assays The EMBO journal High 12356736
2001 Sp3 transcriptional activity is regulated by acetylation; a single lysine residue is responsible for low in vivo activity of Sp3. Sp3 is highly acetylated in vivo, whereas a lysine mutant is not. In an in vitro transcription assay with Sp1/Sp3-depleted HeLa nuclear extract, recombinant Sp3 acts as a strong activator similar to Sp1, indicating that in vivo repression is post-translational. In vitro transcription assay with depleted nuclear extract, site-directed mutagenesis, in vivo acetylation assay, stable insect cell expression of recombinant proteins Nucleic acids research High 11812829
2000 Genetic knockout of mouse Sp3 results in growth retardation, perinatal death due to respiratory failure, and pronounced defect in late tooth formation with impaired ameloblast-specific gene expression; Sp3-null phenotype is distinct from Sp1 knockout, demonstrating non-redundant in vivo functions. Homologous recombination gene knockout in mice, histology, surfactant protein expression analysis, comparison with Sp1 knockout phenotype The EMBO journal High 10675334
2008 SUMO-modified Sp3 bound to DNA provokes local heterochromatic gene silencing by recruiting chromatin remodeller Mi-2, MBT-domain proteins, HP1, and histone methyltransferases SETDB1 and SUV4-20H, leading to H3K9 and H4K20 trimethylation. Chromatin immunoprecipitation (ChIP), reporter assays, sumoylation-competent/deficient Sp3 constructs EMBO reports High 18617891
2002 Sp3 forms a separate complex from Sp1 in breast cancer cells and associates with CK2-phosphorylated HDAC2; protein kinase CK2 is associated with and phosphorylates HDAC2 recruited by Sp3, and alkaline phosphatase treatment reduces HDAC activity in Sp3 complexes. Co-immunoprecipitation, in vitro kinase assay, alkaline phosphatase treatment, chromatin crosslinking The Journal of biological chemistry High 12176973
2017 Sp3 facilitates recruitment of HDAC2 to synaptic plasticity gene promoters in neurons; Sp3 knockdown phenocopies HDAC2 knockdown in reducing synaptic gene expression, and an HDAC2 fragment containing the Sp3-binding domain restores synaptic plasticity in a neurodegeneration mouse model. RNAi knockdown, integrative genomics/ChIP-seq, exogenous HDAC2 fragment rescue in mouse model Cell reports High 28793257
2004 Sp3 is expressed as four isoforms arising from alternative translational start sites at positions 1, 37, 856, and 907; none of the isoforms is glycosylated (unlike Sp1); all four isoforms are SUMO-modified exclusively at lysine 551 in vivo and in vitro; the two long isoforms show promoter-context-dependent transcriptional activity regulated by SUMO modification, while the small isoforms are transcriptionally inactive. Immunoblot analysis in Sp3-deficient cell lines, in vitro SUMO conjugation, mutagenesis, translational initiation mapping, transcriptional reporter assays The Journal of biological chemistry High 15247228
2003 Sp3 binds promoters containing multiple adjacent Sp-binding sites as a more stable multimeric complex compared to monomeric binding at single sites, and this promoter-dependent binding stability enables Sp3 to efficiently compete with Sp1 at multi-site promoters, blocking Sp1 synergistic transactivation without Sp3 itself synergistically activating transcription. EMSA mobility shift analysis, promoter-specific transcription assays, complex stability measurements Nucleic acids research Medium 12954773
2001 Sp3 is required for proper skeletal ossification; both endochondral and intramembranous ossification are impaired in Sp3-/- embryos, osteocalcin expression is reduced, and Sp3-/- ES cells show reduced osteogenic differentiation capacity in vitro despite normal Cbfa1 expression. Sp3 knockout mice analysis, in vitro ES cell osteogenic differentiation, gene expression analysis Mechanisms of development High 11472836
2003 Sp3 is required for normal hematopoiesis; Sp3-/- mice show T-cell developmental arrest, reduced B-cell numbers, and a cell-autonomous defect in erythroid and myeloid engraftment in transplantation assays, with a specific delay in definitive erythropoiesis. Sp3 knockout mice analysis, in vitro differentiation, in vivo bone marrow transplantation assay Blood High 12676787
2007 Sp3-null mice on C57BL/6 background develop severe cardiac malformations including defective heart looping at E10.5 and structural defects by E14.5; ChIP shows Sp3 directly bound to the Carp promoter in vivo, and Carp expression is prematurely downregulated in Sp3-null hearts; Wt1 expression in epicardium-derived cells is also diminished. Sp3 knockout mice cardiac analysis, ChIP assay for Carp promoter occupancy, microarray analysis, marker gene expression panel Molecular and cellular biology High 17923686
2014 Combined conditional knockout of Sp1 and Sp3 in megakaryocytes causes severe macrothrombocytopenia with a cell-autonomous defect in proplatelet formation and a less compact demarcation membrane system; Sp1/Sp3 depletion downregulates cytoskeleton-related proteins including Mylk, and Mylk inhibition phenocopies the proplatelet defect. Pf4-Cre conditional double-knockout mice, flow cytometry, electron microscopy, megakaryocyte transcriptomics, platelet proteomics, Mylk inhibitor treatment Blood High 25538045
2001 c-Myc interacts with Sp1/Sp3 via the central region of c-Myc binding to the zinc finger domain of Sp1/Sp3, and this interaction likely sequesters Sp1/Sp3 to repress p21 promoter activity; the p21 promoter region repressed by Myc contains only Sp1-binding sites and no canonical Myc E-box. Co-immunoprecipitation, GST pulldown, transcriptional reporter assays, 4-OHT-inducible Myc-ER fusion Proceedings of the National Academy of Sciences of the United States of America Medium 11274368
2007 Glutamate receptor activation triggers calpain-mediated cleavage of Sp3 and Sp4 in neurons; purified calpain I cleaves Sp3 into products that retain GC/T-binding activity; this is blocked by calpain inhibitors and observed after cerebral ischemia/reperfusion in vivo. In vitro calpain cleavage assay with purified proteins, calpain inhibitor treatment, in vivo ischemia model, immunofluorescence, western blot Journal of neurochemistry High 17316402
2005 Sp3 interacts with GABPα through its zinc finger DNA-binding domain, and both Sp1 and Sp3 synergistically activate the utrophin promoter together with GABP; physical interaction between Sp factors and GABPα was demonstrated by in vitro binding assays and domain mapping. In vitro protein-protein interaction assays, domain deletion analysis, co-transfection in Drosophila SL2 cells, transcriptional reporter assays Journal of molecular biology Medium 11237613
2002 p300 physically interacts with Sp3 in vivo and in vitro, and cotransfection of p300 elevates Sp3-mediated activation of the p21 promoter; a p300 dominant-negative mutant blocks Sp1- or Sp3-mediated activation, placing p300 as a co-activator of Sp3. Co-immunoprecipitation, in vitro binding assay, dominant-negative p300 co-transfection, reporter assays The Journal of biological chemistry Medium 12071960
2005 Sp1 and Sp3 are organized into distinct non-overlapping nuclear domains in human cells; Sp3 partitions preferentially with the tightly bound nuclear protein fraction and nuclear matrix, while Sp1 and Sp3 associate with different nuclear matrix attachment sites; ChIP/re-ChIP shows Sp1 and Sp3 do not co-occupy the same trefoil factor 1 promoter simultaneously. Indirect immunofluorescence with deconvolution microscopy, nuclear fractionation, nuclear matrix preparation, ChIP and re-ChIP assays Molecular biology of the cell High 15987735
2005 Sumoylation of internally initiated Sp3 isoforms (M1 and M2) is required for their repressive activity; mutation of K551 converts M1 from a repressor into a potent transcriptional activator; Ubc9 (SUMO-1 conjugating enzyme) was identified as an M2-binding protein by yeast two-hybrid. Yeast two-hybrid screen, in vivo SUMO conjugation assay, K551R mutagenesis, transcriptional reporter assays Cellular signalling Medium 15494207
2006 Sp3 acetylation (catalyzed by p300 acetyltransferase) in response to sodium butyrate represses hIGFBP-3 expression; EMSA of nuclei from butyrate-treated cells reveals an extra, slower Sp3-DNA complex recognized by both anti-Sp3 and anti-acetyl-lysine antibodies; E1A (p300 inhibitor) reverses butyrate-induced repression. EMSA with antibody detection, E1A co-transfection, reporter assays, inhibitor treatment Journal of pediatric gastroenterology and nutrition Medium 16456404
2013 NF-κB RELA subunit interacts with SP3 and this RELA-SP3 interaction is enhanced by NF-κB activation (LPS or constitutively active IKKβ); the RELA-SP3 complex suppresses SP1-mediated FGF-10 transcription; the N-terminal region of SP3 is required for its inhibitory function; dominant-negative IκB prevents SP3-mediated FGF-10 inhibition. ChIP of Fgf-10 promoter in LPS-treated cells, co-IP of RELA and SP3, constitutively active/dominant-negative IKK constructs, reporter assays The Journal of biological chemistry Medium 23558680
2010 Sp3 binds the Notch1 gene promoter and represses its transcription in keratinocytes; combined Klf4 and Sp3 knockdown is required to increase Notch1 transcription, indicating overlapping repressor functions through promoter binding. Combined siRNA knockdown, reporter assays with GC-rich promoter, binding analysis PloS one Medium 20442780
2006 Sp3 mRNA is predominant in neurons (compared to Sp1), and Sp3 protein is present at lower levels in glia; calpain cleaves Sp3 into species that retain DNA binding activity, with cleavage also occurring after ischemia/reperfusion in vivo. RT-PCR, western blot, immunofluorescence, DNA-binding supershift assay, purified calpain in vitro cleavage Journal of neurochemistry Medium 17316402
2006 In cortical neurons, Sp3 (along with Sp3/Sp4) is the predominant Sp-family DNA-binding factor rather than Sp1; full-length Sp3 overexpression prevents neuronal death in response to oxidative stress and DNA damage in a DNA-binding-domain-dependent manner. Overexpression of full-length Sp3 vs. zinc-finger-only constructs, neuronal survival assay under oxidative stress, western blot/nuclear fractionation The Journal of neuroscience Medium 12736330
2015 ChIP-seq in mouse embryonic fibroblasts shows Sp1 and Sp3 occupy essentially the same promoters and localize to GC boxes genome-wide; re-expression of Sp3 in knockout MEFs confirms that the zinc finger domain dictates Sp3 genomic binding site selection, distinguishing it from Sp2. ChIP-seq, re-expression in knockout MEFs, zinc-finger deletion mutants PLoS genetics High 25793500
2010 Sp3, together with ATF-2, forms a complex at the ITGB8 (integrin β8) core promoter in a p38 MAPK-dependent manner; Sp3 is required for ITGB8 transcription and protein expression, and SP3 reduction blocks αvβ8-mediated TGF-β activation. ChIP, co-IP showing Sp1/Sp3/AP-1 complex, siRNA knockdown, p38 inhibitor, reporter assays The Journal of biological chemistry Medium 20519498
2019 Sp3 and Sp1 binding sites largely overlap in hematopoietic progenitors by ChIP-seq; Sp3 cooperates with a DNA-binding mutant of Sp1 (Sp1ΔDBD) to enable hematopoiesis, but cannot rescue hematopoiesis in complete absence of Sp1; Sp1 DNA binding is required for proper timing and coordination of differentiation trajectories as revealed by single-cell gene expression analysis. ChIP-seq, genetic complementation in Sp1ΔDBD ES cells, single-cell gene expression analysis, in vitro hematopoietic differentiation Epigenetics & chromatin High 31164147

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1994 Sp1-mediated transcriptional activation is repressed by Sp3. The EMBO journal 676 8070411
2004 Gene regulation by Sp1 and Sp3. Biochemistry and cell biology = Biochimie et biologie cellulaire 353 15284899
2001 Myc represses the p21(WAF1/CIP1) promoter and interacts with Sp1/Sp3. Proceedings of the National Academy of Sciences of the United States of America 348 11274368
2002 SUMO-1 modification represses Sp3 transcriptional activation and modulates its subnuclear localization. Molecular cell 311 12419227
2010 The role of Sp1 and Sp3 in normal and cancer cell biology. Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft 284 20810260
2017 Evaluation of FASP, SP3, and iST Protocols for Proteomic Sample Preparation in the Low Microgram Range. Journal of proteome research 234 28948796
1997 Sp3 encodes multiple proteins that differ in their capacity to stimulate or repress transcription. Nucleic acids research 230 9224612
2020 Automated sample preparation with SP3 for low-input clinical proteomics. Molecular systems biology 225 32129943
2002 Transcription factor Sp3 is silenced through SUMO modification by PIAS1. The EMBO journal 225 12356736
2018 Extending the Compatibility of the SP3 Paramagnetic Bead Processing Approach for Proteomics. Journal of proteome research 212 29565595
2003 Sp1 and Sp3 are oxidative stress-inducible, antideath transcription factors in cortical neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 195 12736330
2000 Transcription factor Sp3 is essential for post-natal survival and late tooth development. The EMBO journal 170 10675334
2002 Oxidative stress regulates vascular endothelial growth factor-A gene transcription through Sp1- and Sp3-dependent activation of two proximal GC-rich promoter elements. The Journal of biological chemistry 165 12509426
2000 p300 collaborates with Sp1 and Sp3 in p21(waf1/cip1) promoter activation induced by histone deacetylase inhibitor. The Journal of biological chemistry 151 10625687
1998 Hypoxia regulates beta-enolase and pyruvate kinase-M promoters by modulating Sp1/Sp3 binding to a conserved GC element. The Journal of biological chemistry 144 9748288
2001 Transcription factor Sp3 is regulated by acetylation. Nucleic acids research 129 11812829
1999 Both Sp1 and Sp3 are responsible for p21waf1 promoter activity induced by histone deacetylase inhibitor in NIH3T3 cells. Journal of cellular biochemistry 129 10321829
1997 Involvement of the Sp3 transcription factor in induction of p21Cip1/WAF1 in keratinocyte differentiation. The Journal of biological chemistry 129 8995437
2001 Cross talk among calcineurin, Sp1/Sp3, and NFAT in control of p21(WAF1/CIP1) expression in keratinocyte differentiation. Proceedings of the National Academy of Sciences of the United States of America 128 11493684
2003 Gap junctional communication modulates gene transcription by altering the recruitment of Sp1 and Sp3 to connexin-response elements in osteoblast promoters. The Journal of biological chemistry 113 12700237
2001 Impaired ossification in mice lacking the transcription factor Sp3. Mechanisms of development 98 11472836
1998 Sp1, but not Sp3, functions to mediate promoter activation by TGF-beta through canonical Sp1 binding sites. Nucleic acids research 95 9580699
2004 Complexity of translationally controlled transcription factor Sp3 isoform expression. The Journal of biological chemistry 92 15247228
1997 Sp3 is a transcriptional activator of the human alpha2(I) collagen gene. Nucleic acids research 91 9278495
2002 Regulation of transcription of the Dnmt1 gene by Sp1 and Sp3 zinc finger proteins. European journal of biochemistry 89 12071960
2014 CpG methylation regulates allelic expression of GDF5 by modulating binding of SP1 and SP3 repressor proteins to the osteoarthritis susceptibility SNP rs143383. Human genetics 85 24861163
2003 Stability of the Sp3-DNA complex is promoter-specific: Sp3 efficiently competes with Sp1 for binding to promoters containing multiple Sp-sites. Nucleic acids research 83 12954773
1997 Transcription factor Sp3 antagonizes activation of the ornithine decarboxylase promoter by Sp1. Nucleic acids research 83 9115370
2017 The Transcription Factor Sp3 Cooperates with HDAC2 to Regulate Synaptic Function and Plasticity in Neurons. Cell reports 81 28793257
2016 Specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 are non-oncogene addiction genes in cancer cells. Oncotarget 81 26967243
2001 Sp3 represses the Sp1-mediated transactivation of the human COL2A1 gene in primary and de-differentiated chondrocytes. The Journal of biological chemistry 80 11447232
2007 Sp1 and Sp3 regulate basal transcription of the survivin gene. Biochemical and biophysical research communications 79 17350596
2002 The transcriptional repressor Sp3 is associated with CK2-phosphorylated histone deacetylase 2. The Journal of biological chemistry 78 12176973
2022 Solvent Precipitation SP3 (SP4) Enhances Recovery for Proteomics Sample Preparation without Magnetic Beads. Analytical chemistry 76 35848328
2008 SUMO-modified Sp3 represses transcription by provoking local heterochromatic gene silencing. EMBO reports 73 18617891
1998 Differential effects of heterogeneous nuclear ribonucleoprotein K on Sp1- and Sp3-mediated transcriptional activation of a neuronal nicotinic acetylcholine receptor promoter. The Journal of biological chemistry 70 9677424
1998 Modulation of human alpha1(I) procollagen gene activity by interaction with Sp1 and Sp3 transcription factors in vitro. Gene 68 9666093
2002 Identification of regulatory elements in the human adipose most abundant gene transcript-1 ( apM-1) promoter: role of SP1/SP3 and TNF-alpha as regulatory pathways. Diabetologia 67 12378384
2005 Specificity of transcriptional regulation by the zinc finger transcription factors Sp1, Sp3, and Egr-1. Journal of cellular biochemistry 64 15523672
2001 Sp1 and Sp3 physically interact and co-operate with GABP for the activation of the utrophin promoter. Journal of molecular biology 64 11237613
2008 An Sp1/Sp3 binding polymorphism confers methylation protection. PLoS genetics 58 18725933
2005 Sp1/Sp3 and the myeloid zinc finger gene MZF1 regulate the human N-cadherin promoter in osteoblasts. Experimental cell research 57 15541732
2017 The miR-491-3p/Sp3/ABCB1 axis attenuates multidrug resistance of hepatocellular carcinoma. Cancer letters 56 28844709
2005 Differential intranuclear organization of transcription factors Sp1 and Sp3. Molecular biology of the cell 56 15987735
2002 Transactivation of the progesterone receptor gene in granulosa cells: evidence that Sp1/Sp3 binding sites in the proximal promoter play a key role in luteinizing hormone inducibility. Molecular endocrinology (Baltimore, Md.) 55 12554796
2015 Sp1 cooperates with Sp3 to upregulate MALAT1 expression in human hepatocellular carcinoma. Oncology reports 54 26352013
2014 Sp1/Sp3 transcription factors regulate hallmarks of megakaryocyte maturation and platelet formation and function. Blood 52 25538045
2005 Sp1 and Sp3 activate transcription of the human dopamine transporter gene. Journal of neurochemistry 52 15816870
1999 GLUT1 glucose transporter gene transcription is repressed by Sp3. Evidence for a regulatory role of Sp3 during myogenesis. Journal of molecular biology 52 10556032
2002 A novel role of Sp1 and Sp3 in the interferon-gamma -mediated suppression of macrophage lipoprotein lipase gene transcription. The Journal of biological chemistry 48 11796707
2009 Protein structure prediction by pro-Sp3-TASSER. Biophysical journal 47 19289038
2001 Novel transcriptional regulation of the human CYP3A7 gene by Sp1 and Sp3 through nuclear factor kappa B-like element. The Journal of biological chemistry 46 11495920
2015 Zinc finger independent genome-wide binding of Sp2 potentiates recruitment of histone-fold protein Nf-y distinguishing it from Sp1 and Sp3. PLoS genetics 45 25793500
2002 Stimulation of vascular endothelial growth factor gene transcription by all trans retinoic acid through Sp1 and Sp3 sites in human bronchioloalveolar carcinoma cells. American journal of respiratory cell and molecular biology 45 11804877
2007 Glutamate receptor activation evokes calpain-mediated degradation of Sp3 and Sp4, the prominent Sp-family transcription factors in neurons. Journal of neurochemistry 44 17316402
2003 E2F and Sp1/Sp3 Synergize but are not sufficient to activate the MYCN gene in neuroblastomas. The Journal of biological chemistry 44 14645238
2001 Regulation of human monoamine oxidase B gene by Sp1 and Sp3. Molecular pharmacology 42 11259630
2007 Transcription factor Sp3 knockout mice display serious cardiac malformations. Molecular and cellular biology 41 17923686
2004 Regulation of the human secretin gene is controlled by the combined effects of CpG methylation, Sp1/Sp3 ratio, and the E-box element. Molecular endocrinology (Baltimore, Md.) 40 15118068
2004 Concentration-dependent effects of endogenous S-nitrosoglutathione on gene regulation by specificity proteins Sp3 and Sp1. The Biochemical journal 39 14766015
2003 Impaired hematopoiesis in mice lacking the transcription factor Sp3. Blood 39 12676787
2003 Regulation of the integrin subunit alpha5 gene promoter by the transcription factors Sp1/Sp3 is influenced by the cell density in rabbit corneal epithelial cells. Investigative ophthalmology & visual science 38 12939287
2000 Sp1 and Sp3 transactivate the RET proto-oncogene promoter. Gene 38 11054558
2003 Influence of sp1/sp3 expression on corneal epithelial cells proliferation and differentiation properties in reconstructed tissues. Investigative ophthalmology & visual science 37 12657578
2010 Differential control of Notch1 gene transcription by Klf4 and Sp3 transcription factors in normal versus cancer-derived keratinocytes. PloS one 36 20442780
2006 Sp1 and Sp3 foci distribution throughout mitosis. Journal of cell science 36 16492704
2004 Dystrophin Dp71 expression is down-regulated during myogenesis: role of Sp1 and Sp3 on the Dp71 promoter activity. The Journal of biological chemistry 36 15550398
2003 Sp1 and Sp3 transcription factors are required for trans-activation of the human SERCA2 promoter in cardiomyocytes. Cardiovascular research 36 14613864
2013 Interactions between NF-κB and SP3 connect inflammatory signaling with reduced FGF-10 expression. The Journal of biological chemistry 35 23558680
2007 Butyrate induces intestinal sodium absorption via Sp3-mediated transcriptional up-regulation of epithelial sodium channels. Gastroenterology 35 17241874
2005 Regulation of cytochrome b5 gene transcription by Sp3, GATA-6, and steroidogenic factor 1 in human adrenal NCI-H295A cells. Molecular endocrinology (Baltimore, Md.) 35 15831526
2023 Angiotensin-converting enzyme inhibitor promotes angiogenesis through Sp1/Sp3-mediated inhibition of notch signaling in male mice. Nature communications 34 36759621
2003 Oncogenic Ha-Ras transformation modulates the transcription of the CTP:phosphocholine cytidylyltransferase alpha gene via p42/44MAPK and transcription factor Sp3. The Journal of biological chemistry 33 12584202
2022 SP3-Enabled Rapid and High Coverage Chemoproteomic Identification of Cell-State-Dependent Redox-Sensitive Cysteines. Molecular & cellular proteomics : MCP 32 35219905
2009 Dual role of Sp3 transcription factor as an inducer of apoptosis and a marker of tumour aggressiveness. PloS one 32 19212434
2006 Sodium butyrate-mediated Sp3 acetylation represses human insulin-like growth factor binding protein-3 expression in intestinal epithelial cells. Journal of pediatric gastroenterology and nutrition 32 16456404
2006 NF-Y and Sp1/Sp3 are involved in the transcriptional regulation of the peptidylarginine deiminase type III gene (PADI3) in human keratinocytes. The Biochemical journal 32 16671893
2005 SP3/SP1 transcription activity regulates specific expression of collagen type X in hypertrophic chondrocytes. The Journal of biological chemistry 32 15849196
2000 spr-2, a suppressor of the egg-laying defect caused by loss of sel-12 presenilin in Caenorhabditis elegans, is a member of the SET protein subfamily. Proceedings of the National Academy of Sciences of the United States of America 32 11114162
2008 Transcription factors sp1 and sp3 regulate expression of human extracellular superoxide dismutase in lung fibroblasts. American journal of respiratory cell and molecular biology 31 18314536
2007 Regulation of the dual-function transcription factor Sp3 by SUMO. Biochemical Society transactions 31 18031229
2002 Characterization of human cathepsin L promoter and identification of binding sites for NF-Y, Sp1 and Sp3 that are essential for its activity. The Biochemical journal 31 11742542
2012 Predictive value of Sp1/Sp3/FLIP signature for prostate cancer recurrence. PloS one 30 23028678
2007 Involvement of Sp1 and Sp3 in differential regulation of human NHE3 promoter activity by sodium butyrate and IFN-gamma/TNF-alpha. American journal of physiology. Gastrointestinal and liver physiology 30 17540780
2003 Regulation of renin enhancer activity by nuclear factor I and Sp1/Sp3. Biochimica et biophysica acta 30 12591615
1996 Distal Sp3 binding sites in the hIGBP-1 gene promoter suppress transcriptional repression in decidualized human endometrial stromal cells: identification of a novel Sp3 form in decidual cells. Molecular endocrinology (Baltimore, Md.) 30 8776721
2005 Sumoylation of internally initiated Sp3 isoforms regulates transcriptional repression via a Trichostatin A-insensitive mechanism. Cellular signalling 29 15494207
2007 Sp1 and Sp3 regulate basal transcription of the human APOBEC3G gene. Nucleic acids research 28 17517765
2005 Molecular basis for keratoconus: lack of TrkA expression and its transcriptional repression by Sp3. Proceedings of the National Academy of Sciences of the United States of America 28 16275928
2004 Sp3 repression of polymorphic human NRH:quinone oxidoreductase 2 gene promoter. Free radical biology & medicine 28 15451063
2003 Functional characterization of transcription factor binding sites for HNF1-alpha, HNF3-beta (FOXA2), HNF4-alpha, Sp1 and Sp3 in the human prothrombin gene enhancer. Journal of thrombosis and haemostasis : JTH 27 12911579
1999 Binding of Sp1 and Sp3 transcription factors to the Oct-4 gene promoter. Cellular and molecular biology (Noisy-le-Grand, France) 27 10512200
2010 Transcription of the transforming growth factor beta activating integrin beta8 subunit is regulated by SP3, AP-1, and the p38 pathway. The Journal of biological chemistry 26 20519498
2006 Regulation of neurotrophin-3 gene transcription by Sp3 and Sp4 in neurons. Journal of neurochemistry 26 17059557
1998 Binding and functional effects of transcription factors Sp1 and Sp3 on the proximal human lecithin:cholesterol acyltransferase promoter. Journal of lipid research 26 9610763
2020 ZEB1 Mediates Fibrosis in Corneal Endothelial Mesenchymal Transition Through SP1 and SP3. Investigative ophthalmology & visual science 25 32721022
2019 Robust hematopoietic specification requires the ubiquitous Sp1 and Sp3 transcription factors. Epigenetics & chromatin 25 31164147
2006 Hydroxyurea and interleukin-6 synergistically reactivate HIV-1 replication in a latently infected promonocytic cell line via SP1/SP3 transcription factors. The Journal of biological chemistry 24 17150965
1999 Perinatal regulation of the ClC-2 chloride channel in lung is mediated by Sp1 and Sp3. The American journal of physiology 24 10198359
2000 MRG1 expression in fibroblasts is regulated by Sp1/Sp3 and an Ets transcription factor. The Journal of biological chemistry 23 11114295