Affinage

SP3

Transcription factor Sp3 · UniProt Q02447

Length
781 aa
Mass
81.9 kDa
Annotated
2026-06-10
100 papers in source corpus 31 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SP3 is a ubiquitously expressed GC-box-binding zinc-finger transcription factor that acts as a bifunctional regulator, repressing or activating target genes depending on post-translational state and promoter context (PMID:8070411, PMID:12837748). Its repressor function operates through at least two routes: direct competition with Sp1 for shared GC-box sites — including the formation of unusually stable multimeric SP3-DNA complexes at promoters with adjacent Sp sites that block Sp1 synergy (PMID:8070411, PMID:12954773) — and a portable N-terminal repression domain that acts independently of DNA binding by contacting the general transcription machinery (PMID:8621476). SP3 also produces internally initiated 80 kDa isoforms that retain GC-box binding but lack activation capacity and act as dominant inhibitors of Sp1/SP3-driven transcription (PMID:9224612). SP3 activity is set by competing modifications: acetylation by p300 at a single lysine converts SP3 into a strong activator, whereas SUMOylation at K551 — catalyzed by the E3 ligase PIAS1 acting with Ubc9 — silences SP3 and nucleates heterochromatin by recruiting Mi-2, HP1, SETDB1, and SUV4-20H with attendant H3K9/H4K20 trimethylation (PMID:11812829, PMID:12837748, PMID:12356736, PMID:15494207, PMID:18617891). SP3 partitions into distinct, non-overlapping nuclear domains from Sp1 and associates with HDAC1/2 corepressor complexes to enforce promoter hypoacetylation (PMID:15987735, PMID:12176973, PMID:25972164). In vivo knockout studies establish non-redundant developmental roles in tooth and enamel formation, skeletal ossification, cardiac morphogenesis, and erythroid/myeloid hematopoiesis, with combined Sp1/SP3 loss required for defects in megakaryocyte proplatelet formation and endothelial angiogenesis (PMID:10675334, PMID:11472836, PMID:12676787, PMID:17923686, PMID:25538045, PMID:36759621).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1994 High

    Established the founding mechanism of SP3 as a repressor — whether it antagonizes Sp1 by site competition rather than by a separate effector activity.

    Evidence Co-transfection in mammalian and Drosophila SL2 cells with DNA-binding-domain mutants and Sp1/SP3 chimeras

    PMID:8070411

    Open questions at the time
    • Did not identify protein partners mediating repression beyond competition
    • Did not address context-dependent activation
  2. 1996 High

    Showed SP3 carries an autonomous repression activity, not merely passive site occupancy, by demonstrating a portable N-terminal domain that represses when tethered independently of the zinc fingers.

    Evidence DNA and RNA tethering of SP3 fusion proteins in co-transfection assays

    PMID:8621476

    Open questions at the time
    • Specific general-transcription-machinery contacts not biochemically defined
  3. 1997 High

    Resolved the molecular basis of SP3 functional heterogeneity by demonstrating internally initiated short isoforms that bind DNA but inhibit rather than activate.

    Evidence Internal translation initiation site mapping, in vitro DNA binding, and co-transfection

    PMID:9224612

    Open questions at the time
    • Physiological ratio control of isoforms not established
    • Isoform-specific gene targets not defined
  4. 2000 High

    Provided the first in vivo demonstration that SP3 is essential and non-redundant, defining roles in late tooth development and post-natal survival distinct from Sp1.

    Evidence Sp3-null mouse knockout with histology and target gene expression analysis

    PMID:10675334

    Open questions at the time
    • Direct SP3 target genes in ameloblasts not mapped
    • Degree of Sp1 redundancy quantified only qualitatively
  5. 2001 High

    Extended SP3's developmental requirement to skeletal ossification and placed it downstream of or parallel to Cbfa1 in bone formation.

    Evidence Sp3-null embryo histology, osteocalcin expression, and in vitro ES cell osteogenic differentiation

    PMID:11472836

    Open questions at the time
    • Direct osteoblast target promoters not identified
  6. 2002 High

    Identified acetylation as a switch and SUMOylation/PIAS1 as the silencing system, explaining how a single factor toggles between activator and repressor.

    Evidence In vivo/in vitro SUMO conjugation assays, PIAS1/Ubc9 co-IP, single-lysine mutagenesis, and in vitro transcription with depleted nuclear extract

    PMID:11812829 PMID:12356736

    Open questions at the time
    • Crosstalk between acetylation and SUMOylation on the same residue context not fully resolved
    • Stimulus that sets the modification balance not defined here
  7. 2002 High

    Linked SP3 to HDAC corepressor machinery and showed CK2-phosphorylated HDAC2 is enriched in Sp1/SP3 complexes, connecting kinase signaling to SP3-associated deacetylase activity.

    Evidence Reciprocal co-IP, in situ cross-linking, CK2 kinase and phosphatase assays in breast cancer cells

    PMID:12176973

    Open questions at the time
    • Functional consequence of HDAC2 phosphorylation on specific SP3 targets not shown
  8. 2003 High

    Demonstrated p300-mediated acetylation is required for SP3 to function as an activator, defining the molecular basis of its repressor/activator duality.

    Evidence p300 HAT assay, HAT-domain-deleted dominant-negative control, and reporter assays in Sp3-deficient cells

    PMID:12837748

    Open questions at the time
    • Promoter features dictating activator versus repressor outcome not generalized
  9. 2003 High

    Established cell-autonomous requirements for SP3 across hematopoietic lineages, separating its in vivo blood functions from those of Sp1.

    Evidence Sp3-null fetal liver transplantation and in vitro differentiation assays

    PMID:12676787

    Open questions at the time
    • Lineage-specific direct targets not identified
  10. 2003 Medium

    Broadened the SP3 interactome to oncogenic and gene-specific contexts — c-Myc sequestration of Sp1/SP3 and IFN-dependent SP3-specific recruitment of STAT1/STAT2 at the PKR promoter.

    Evidence Co-IP and GST pulldown (c-Myc); EMSA, oligo pulldown, and ChIP under IFN treatment (PKR)

    PMID:11274368 PMID:12954221

    Open questions at the time
    • c-Myc SP3 contact inferred from Sp1/SP3 complex, not direct
    • Inducible versus basal partitioning mechanism at the KCS element unresolved
  11. 2005 High

    Showed Sp1 and SP3 occupy spatially and physically distinct nuclear and chromatin compartments, and that SUMOylation of DNA-bound short isoforms (with Ubc9) drives TSA-insensitive repression.

    Evidence Deconvolution immunofluorescence, nuclear fractionation, re-ChIP; yeast two-hybrid and K551 mutagenesis

    PMID:15494207 PMID:15987735

    Open questions at the time
    • Mechanism keeping Sp1 and SP3 on separate promoter molecules unknown
    • Determinants of compartment partitioning not defined
  12. 2007 High

    Defined a direct developmental SP3 target by showing SP3 binds the Carp promoter and is required for cardiac looping and morphogenesis.

    Evidence Sp3-null mouse phenotyping, ChIP at the Carp promoter, and microarray

    PMID:17923686

    Open questions at the time
    • Whether SP3 acts as activator or repressor at Carp in vivo not fully resolved
  13. 2008 High

    Provided the chromatin mechanism of SUMO-dependent silencing by showing DNA-bound SUMOylated SP3 nucleates heterochromatin through Mi-2, HP1, SETDB1, and SUV4-20H with H3K9/H4K20 trimethylation.

    Evidence ChIP for chromatin factors and histone marks on SUMO-modified SP3

    PMID:18617891

    Open questions at the time
    • Order and dependency of factor recruitment not dissected
    • Reversibility kinetics not characterized
  14. 2014 High

    Revealed functional redundancy with Sp1 in megakaryocytes, where only combined loss disrupts the demarcation membrane system and proplatelet formation via downregulated cytoskeletal genes and MYLK.

    Evidence Conditional Sp1/Sp3 double-knockout mice (two Cre models), EM, transcriptomics, and platelet proteomics

    PMID:25538045

    Open questions at the time
    • Direct SP3 binding at cytoskeletal/MYLK loci not shown
    • SP3-specific contribution versus Sp1 not separated
  15. 2023 High

    Connected SP3 to endothelial angiogenesis control, showing SP3 enhances Sp1-mediated Notch1 promoter repression and that USP7 and HDAC1 regulate Sp1/SP3 in this axis.

    Evidence Endothelial-specific Sp1/Sp3 double-knockout mice, ChIP at Notch1, co-IP for USP7 binding, retinal and tumor angiogenesis models

    PMID:36759621

    Open questions at the time
    • Independent SP3 promoter occupancy distinct from Sp1 not isolated
    • Mechanism of USP7 selectivity for Sp1/SP3 unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the acetylation/SUMOylation/phosphorylation code, isoform ratios, and Sp1 redundancy are integrated to select activator versus repressor output at individual native promoters remains unresolved.
  • No unified model linking modification state to genome-wide target outcome
  • SP3-specific direct targets distinct from Sp1 largely undefined
  • Structural basis of multimeric SP3-DNA complexes unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 4 GO:0003677 DNA binding 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0000228 nuclear chromosome 2 GO:0005634 nucleus 2
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-4839726 Chromatin organization 2
Partners
EP300HDAC2MYCPIAS1RELASP1UBE2IUSP7
Complex memberships
HDAC1/2 corepressor complexREST/HDAC1/HDAC2 repressor complex

Evidence

Reading pass · 31 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 DNA binding sites; an Sp3 mutant lacking the DNA-binding domain does not repress Sp1, indicating competition for binding sites is the mechanism. Chimeric protein experiments showed neither the glutamine-rich domains A/B nor domain D of Sp1 can be replaced by homologous Sp3 regions to restore activation. Co-transfection in mammalian cells and Drosophila SL2 cells; chimeric protein constructs; antibody characterization The EMBO journal High 8070411
1996 Sp3 contains a portable repression domain in its amino-terminal region that functions independently of the zinc finger DNA-binding domain; when tethered to a promoter via a heterologous DNA-binding domain or targeted to promoter-proximal RNA, Sp3 represses transcriptional activation by different positive regulators, suggesting repression occurs through protein-protein interaction with components of the general transcription complex. Fusion protein tethering to promoter DNA; RNA tethering assay; co-transfection in mammalian cells The Journal of biological chemistry High 8621476
1997 Sp3 encodes multiple proteins (115 kDa full-length and 80 kDa isoforms) arising from translational initiation at two internal sites within the Sp3 trans-activation domain; the internally initiated isoforms bind GC-box DNA but lack transcriptional activation capacity and instead function as potent inhibitors of Sp1/Sp3-mediated transcription. Identification of internal translation initiation sites; in vitro binding assays; co-transfection in mammalian and SL2 cells Nucleic acids research High 9224612
2001 Sp3 transcriptional activity is regulated by acetylation; a single lysine residue is responsible for low transcriptional activity of Sp3 in vivo, and Sp3 (but not a lysine-deficient mutant) is highly acetylated in vivo. In an in vitro transcription assay using Sp1/Sp3-depleted HeLa nuclear extract, recombinant Sp3 acts as a strong activator comparable to Sp1. In vitro transcription assay; mutational analysis; in vivo acetylation detection; stable transfection of insect cells for recombinant protein Nucleic acids research High 11812829
2002 Sp3 is SUMOylated in vivo and in vitro at a single lysine within the sequence IKXE located between the second glutamine-rich activation domain and the DNA-binding domain; PIAS1 acts as an E3 SUMO ligase for Sp3 by interacting with both Sp3 and Ubc9 and strongly stimulating SUMO conjugation to Sp3. All mutations that prevented SUMOylation strongly enhanced Sp3 transcriptional activity, demonstrating that SUMO modification silences Sp3. DNA-bound Sp3 does not act as a substrate for SUMO modification. In vivo and in vitro SUMO conjugation assays; mutational analysis; co-immunoprecipitation identifying PIAS1 as E3 ligase; co-transfection transcription assays The EMBO journal High 12356736
2002 Sp1 and Sp3 form separate complexes in estrogen-dependent breast cancer cells; both complexes associate with histone deacetylases (HDACs) 1 and 2. The HDAC2 bound to Sp1 and Sp3 complexes is highly enriched in a CK2-phosphorylated form, and protein kinase CK2 is associated with and phosphorylates HDAC2. Alkaline phosphatase treatment reduces HDAC activity in these complexes. Co-immunoprecipitation; in situ cross-linking; CK2 kinase assay; alkaline phosphatase treatment The Journal of biological chemistry High 12176973
2003 Acetylated Sp3 functions as a transcriptional activator; histone acetyltransferase p300 acetylates Sp3, and p300-mediated acetylation of Sp3 is required for its activator function. Wild-type p300 but not HAT-domain-deleted p300 stimulates Sp3-mediated promoter activity, demonstrating acetylation as a switch controlling Sp3 repressor/activator duality. HAT assay with p300; dominant-negative p300 mutant; co-transfection reporter assays; ectopic Sp3 expression in Sp3-deficient cells The Journal of biological chemistry High 12837748
2003 c-Myc interacts directly with Sp1/Sp3 complexes; the central region of c-Myc interacts with the zinc finger domain of Sp1, and c-Myc co-immunoprecipitates with Sp1/Sp3. This interaction may contribute to Myc-mediated repression of the p21 promoter by sequestering Sp1/Sp3. Co-immunoprecipitation; GST pulldown assay; co-transfection reporter assays Proceedings of the National Academy of Sciences of the United States of America Medium 11274368
2003 The 116 kDa Sp3 polypeptide binds as a monomer to a single Sp-binding site but forms more stable, slower-migrating complexes at adjacent Sp-binding sites. These multimeric Sp3-DNA complexes are significantly more stable than monomeric Sp3-DNA or multimeric Sp1-DNA complexes, allowing Sp3 to compete with Sp1 for promoters containing multiple Sp sites and thereby block Sp1 synergistic transactivation. Electrophoretic mobility shift assay (EMSA); competition binding assays; co-transfection reporter assays Nucleic acids research Medium 12954773
2005 Sp1 and Sp3 are organized into distinct, non-overlapping nuclear domains in human breast and ovarian cells; Sp3 partitions with the tightly bound nuclear protein fraction whereas only a subpopulation of Sp1 does so. Both are bound to the nuclear matrix at different sites. Re-ChIP assays show that although Sp1 and Sp3 both bind the trefoil factor 1 (TFF1) promoter, they do not occupy the same promoter molecule simultaneously. Indirect immunofluorescence microscopy with deconvolution; nuclear fractionation; chromatin immunoprecipitation (ChIP) and re-ChIP Molecular biology of the cell High 15987735
2005 Sumoylation of internally initiated Sp3 isoforms (M1 and M2) plays an important role in transcriptional repression; Ubc9 (SUMO-1 conjugating enzyme) was identified as an M2-binding protein by yeast two-hybrid. Mutation of lysine-551 blocks sumoylation of all Sp3 isoforms and converts M1 into a potent transcriptional activator; the repression is insensitive to the HDAC inhibitor trichostatin A. Yeast two-hybrid screen; Western blot with SUMO-1 antiserum; co-transfection with epitope-tagged SUMO-1; site-directed mutagenesis; reporter assays Cellular signalling High 15494207
2006 Sp1 and Sp3 are displaced from condensed chromosomes during mitosis and maintain separate punctate distributions throughout the mitotic process; in metaphase both Sp1 and Sp3 foci show high colocalization with microfilaments (F-actin), suggesting actin involvement in organizing Sp1/Sp3 foci during mitosis. Sp3 re-enters newly formed nuclei prior to Sp1 in late telophase, and both enter before RNA polymerase II. Indirect immunofluorescence microscopy; image deconvolution; Western blot for protein levels during mitosis Journal of cell science Medium 16492704
2008 SUMOylation of transcription factors including Sp3, when bound to DNA, provokes establishment of compacted repressive chromatin with heterochromatic characteristics; SUMO-dependent recruitment of chromatin remodeler Mi-2, MBT-domain proteins, heterochromatic protein 1 (HP1), and histone methyltransferases SETDB1 and SUV4-20H is induced, concomitant with H3K9 and H4K20 trimethylation. Chromatin immunoprecipitation (ChIP); analysis of histone modifications; functional analysis of SUMO-modified Sp3 EMBO reports High 18617891
2017 Sp3 facilitates recruitment of HDAC2 to synaptic plasticity genes; knockdown of Sp3 phenocopies HDAC2 knockdown by de-repressing synaptic gene expression. An HDAC2 fragment containing the Sp3-binding domain is sufficient to restore synaptic plasticity and memory in a mouse neurodegeneration model. Integrative genomics; siRNA knockdown; functional screening; viral vector-mediated gene delivery in mouse model Cell reports Medium 28793257
2000 Sp3 is required for late tooth development and post-natal survival; Sp3-null mice die at birth of respiratory failure and display pronounced defects in ameloblast-specific gene expression and dentin/enamel formation. Comparison with Sp1 knockout demonstrates distinct in vivo functions with partial redundancy. Homologous recombination (gene knockout in mice); histological analysis; gene expression analysis The EMBO journal High 10675334
2001 Sp3 is required for proper skeletal ossification; both endochondral and intramembranous ossification are impaired in Sp3-null embryos. Reduced osteocalcin expression reflects impaired osteoblast function. Cbfa1 expression is normal in Sp3-null mice, placing Sp3 downstream of or parallel to Cbfa1 in the bone formation pathway. Sp3-null ES cells show reduced capacity for osteogenic differentiation in vitro. Sp3 knockout mouse analysis; in vitro ES cell osteogenic differentiation; gene expression analysis; histology Mechanisms of development High 11472836
2003 Sp3 is required for normal erythroid and myeloid hematopoiesis in a cell-autonomous manner; Sp3-null fetal liver cells fail to engraft the erythroid and myeloid lineages in transplantation assays. Sp3-null mice also show partial arrest of T-cell development and reduced B-cell numbers. Sp3 knockout mouse analysis; in vivo bone marrow transplantation assay; in vitro differentiation assays Blood High 12676787
2007 Sp3 is required for normal cardiac development; Sp3-null hearts display defective looping at E10.5 and severe cardiac malformations at E14.5. Sp3 directly binds the Carp (cardiac ankyrin repeat protein) promoter in vivo and regulates its expression; Wt1 expression in epicardium-derived cells is diminished in Sp3-null hearts. Sp3 knockout mouse analysis (C57BL/6 background); chromatin immunoprecipitation (ChIP); microarray analysis; expression pattern analysis Molecular and cellular biology High 17923686
2014 Simultaneous loss of both Sp1 and Sp3 (but not either alone) in megakaryocytes causes severe macrothrombocytopenia in a cell-autonomous manner; double-knockout megakaryocytes display a less compact demarcation membrane system and striking inability to form proplatelets. Sp1/Sp3 depletion downregulates cytoskeleton-related proteins and MYLK kinase, providing a mechanistic link to proplatelet defects. Conditional double-knockout mice (Mx1-Cre and Pf4-Cre); flow cytometry; electron microscopy; megakaryocyte transcriptomics; platelet proteomics Blood High 25538045
2003 Sp1 and Sp3 are induced by oxidative stress in cortical neurons; sustained high-level expression of full-length Sp1 or full-length Sp3 (but not the Sp1 zinc finger domain alone) prevents neuronal death in response to oxidative stress, DNA damage, or both, establishing them as antideath transcription factors in neurons. Oxidative stress induction; Western blot; HSV vector-mediated overexpression; survival assays in cortical neurons and in vivo rodent models The Journal of neuroscience Medium 12736330
2015 Sp3, together with REST and HDAC1/HDAC2, forms a repressor complex on the ncx1 brain promoter during ischemia, leading to promoter hypoacetylation and reduced NCX1 expression. In contrast, the Sp1/HIF-1/p300 complex activates the same promoter during ischemic preconditioning with concomitant hyperacetylation. Chromatin immunoprecipitation (ChIP); siRNA knockdown; oxygen-glucose deprivation model; in vivo middle cerebral artery occlusion model; pharmacological HDAC inhibition The Journal of neuroscience Medium 25972164
2013 NF-κB RELA subunit interacts with SP3 and recruits it to the Fgf-10 promoter during inflammatory signaling; SP3 co-expression reduces SP1-mediated Fgf-10 promoter activity, and increased RELA-SP3 nuclear interactions correlate with reduced FGF-10 expression. The inhibitory function of SP3 requires sequences in the N-terminal region of the protein. Chromatin immunoprecipitation; co-immunoprecipitation; dominant-negative IκB constructs; constitutively active IKKβ; co-transfection reporter assays The Journal of biological chemistry Medium 23558680
2018 p300 acetyltransferase activity and Sp3 acetylation are regulated by sodium butyrate; butyrate increases acetylation of Sp3 (detected by anti-acetyl-lysine antibody in EMSA), and p300 acetyltransferase inhibition by E1A reverses butyrate-induced repression of hIGFBP-3, linking Sp3 acetylation by p300 to transcriptional repression of hIGFBP-3. EMSA with anti-acetyl-lysine antibody; E1A co-transfection; reporter assays; protein synthesis inhibition Journal of pediatric gastroenterology and nutrition Medium 16456404
2002 The transcriptional coactivator p300 interacts with Sp3 in vivo and in vitro and activates the Dnmt1 promoter in the presence of Sp3; co-transfection of p300 enhances Sp3-mediated transcription from the Dnmt1 promoter. Co-immunoprecipitation (in vivo and in vitro); co-transfection reporter assay in Drosophila SL2 cells European journal of biochemistry Medium 12071960
2001 Both Sp1 and Sp3 physically interact with the GABPα subunit through their zinc finger DNA-binding domains; this interaction mediates synergistic activation of the utrophin promoter by Sp1/Sp3 together with GABP. In vitro pull-down (physical interaction); co-transfection in Drosophila SL2 cells; functional domain deletion analysis Journal of molecular biology Medium 11237613
2016 Butyrate activates two different protein kinase C isoforms that differentially phosphorylate Sp1 (dephosphorylation via serine/threonine phosphatases) and Sp3 (phosphorylation via ERK-MAPK); Sp1 dephosphorylation causes its displacement from the TLR5 promoter, while Sp3 phosphorylation promotes its binding and recruitment of p300 with histone acetylation and transcriptional activation. ChIP; EMSA; PKC isoform inhibitors; ERK-MAPK inhibition; phosphatase treatment; reporter assays; siRNA knockdown Nucleic acids research Medium 27060138
2023 USP7, activated by ACE inhibitor treatment, translocates to the nucleus and binds Sp1/Sp3; HDAC1 deacetylates Sp1/Sp3. Endothelial Sp1 binds the Notch1 promoter and inhibits its transcription, with Sp3 enhancing this repression; endothelial-specific Sp1/Sp3 double-knockout reduces angiogenesis and activates the Notch1/VEGFR2 pathway. Endothelial-specific conditional knockout mice; chromatin immunoprecipitation; co-immunoprecipitation; retinal and tumor angiogenesis models Nature communications High 36759621
2005 Ceramide reduces Sp3 acetylation and increases the Sp3/Sp1 ratio on the hTERT promoter, enhancing Sp3 repressor function. Ceramide reduces Sp1 binding and increases Sp3 binding to the hTERT promoter, resulting in reduced RNA polymerase II recruitment. Chromatin immunoprecipitation; EMSA; co-transfection reporter assays; siRNA knockdown of Sp1 The Journal of biological chemistry Medium 15951564
2010 Klf4 and Sp3 bind to the Notch1 promoter in keratinocytes and both function as overlapping transcriptional repressors; combined knockdown of Klf4 and Sp3 is required to increase Notch1 transcription, whereas knockdown of either alone is insufficient. ChIP; siRNA knockdown; reporter assays; overexpression studies PloS one Medium 20442780
2003 Only Sp3 (not Sp1) is a constituent of the interferon-inducible iKIBP complexes at the PKR promoter; Sp3 binding at the KCS element in vivo is IFN-dependent, whereas Sp1 binding is not. Sp3 within the iKIBP complex recruits STAT1 and STAT2 to the KCS element in an IFN-dependent manner, implicating Sp3 specifically in inducible (not basal) PKR transcription. EMSA; oligonucleotide pull-down; chromatin immunoprecipitation; IFN treatment Virology Medium 12954221
2019 Sp1 and Sp3 binding sites largely overlap at chromatin in hematopoietic development; Sp3 cooperates with the Sp1 DNA-binding mutant (Sp1ΔDBD) to enable hematopoiesis but cannot substitute in the complete absence of Sp1. Stable chromatin binding of Sp1 is required to maintain robust differentiation trajectories, as loss of Sp1 DNA binding leads to distortion of cell fate decision timing. Embryonic stem cell differentiation; single-cell gene expression analysis; chromatin accessibility assays; Sp1 DNA-binding domain mutant cells Epigenetics & chromatin Medium 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 354 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 352 11274368
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
2020 Automated sample preparation with SP3 for low-input clinical proteomics. Molecular systems biology 232 32129943
1997 Sp3 encodes multiple proteins that differ in their capacity to stimulate or repress transcription. Nucleic acids research 230 9224612
2002 Transcription factor Sp3 is silenced through SUMO modification by PIAS1. The EMBO journal 226 12356736
2018 Extending the Compatibility of the SP3 Paramagnetic Bead Processing Approach for Proteomics. Journal of proteome research 217 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
2001 Transcription factor Sp3 is regulated by acetylation. Nucleic acids research 129 11812829
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
1998 Transcription factors Sp1 and Sp3 alter vascular endothelial growth factor receptor expression through a novel recognition sequence. The Journal of biological chemistry 122 9668119
2003 Acetylated sp3 is a transcriptional activator. The Journal of biological chemistry 110 12837748
2001 Impaired ossification in mice lacking the transcription factor Sp3. Mechanisms of development 98 11472836
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
2015 Sp3/REST/HDAC1/HDAC2 Complex Represses and Sp1/HIF-1/p300 Complex Activates ncx1 Gene Transcription, in Brain Ischemia and in Ischemic Brain Preconditioning, by Epigenetic Mechanism. The Journal of neuroscience : the official journal of the Society for Neuroscience 85 25972164
2001 TNF-alpha downregulates murine hepatic growth hormone receptor expression by inhibiting Sp1 and Sp3 binding. The Journal of clinical investigation 84 11390427
2017 The Transcription Factor Sp3 Cooperates with HDAC2 to Regulate Synaptic Function and Plasticity in Neurons. Cell reports 83 28793257
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
2022 Solvent Precipitation SP3 (SP4) Enhances Recovery for Proteomics Sample Preparation without Magnetic Beads. Analytical chemistry 82 35848328
2016 Specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 are non-oncogene addiction genes in cancer cells. Oncotarget 82 26967243
2018 E2F1/SP3/STAT6 axis is required for IL-4-induced epithelial-mesenchymal transition of colorectal cancer cells. International journal of oncology 81 29901191
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
1997 Sp1 and Sp3 regulate expression of the neuronal nicotinic acetylcholine receptor beta4 subunit gene. The Journal of biological chemistry 79 9325332
1996 Sp3 represses transcription when tethered to promoter DNA or targeted to promoter proximal RNA. The Journal of biological chemistry 79 8621476
2008 The human receptor tyrosine kinase Axl gene--promoter characterization and regulation of constitutive expression by Sp1, Sp3 and CpG methylation. Bioscience reports 78 18522535
2002 The transcriptional repressor Sp3 is associated with CK2-phosphorylated histone deacetylase 2. The Journal of biological chemistry 78 12176973
2008 SUMO-modified Sp3 represses transcription by provoking local heterochromatic gene silencing. EMBO reports 74 18617891
2000 Sp1 and Sp3 activate p21 (WAF1/CIP1) gene transcription in the Caco-2 colon adenocarcinoma cell line. Oncogene 72 11064455
2021 SP3-FAIMS Chemoproteomics for High-Coverage Profiling of the Human Cysteinome*. Chembiochem : a European journal of chemical biology 67 33442901
2001 Sp1 and Sp3 physically interact and co-operate with GABP for the activation of the utrophin promoter. Journal of molecular biology 64 11237613
1997 The human POLD1 gene. Identification of an upstream activator sequence, activation by Sp1 and Sp3, and cell cycle regulation. The Journal of biological chemistry 61 9030545
2017 The miR-491-3p/Sp3/ABCB1 axis attenuates multidrug resistance of hepatocellular carcinoma. Cancer letters 57 28844709
2005 Sp1/Sp3 and the myeloid zinc finger gene MZF1 regulate the human N-cadherin promoter in osteoblasts. Experimental cell research 57 15541732
2011 The p65 subunit of NF-κB inhibits COL1A1 gene transcription in human dermal and scleroderma fibroblasts through its recruitment on promoter by protein interaction with transcriptional activators (c-Krox, Sp1, and Sp3). The Journal of biological chemistry 56 22139845
2005 Differential intranuclear organization of transcription factors Sp1 and Sp3. Molecular biology of the cell 56 15987735
2015 Sp1 cooperates with Sp3 to upregulate MALAT1 expression in human hepatocellular carcinoma. Oncology reports 54 26352013
2006 Role of cyclooxygenase-2 induction by transcription factor Sp1 and Sp3 in neuronal oxidative and DNA damage response. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 54 17012241
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
2007 Sp1/Sp3 and DNA-methylation contribute to basal transcriptional activation of human podoplanin in MG63 versus Saos-2 osteoblastic cells. BMC molecular biology 51 17343736
2000 ZIC2 and Sp3 repress Sp1-induced activation of the human D1A dopamine receptor gene. The Journal of biological chemistry 51 10984499
2003 Decreased methylation and transcription repressor Sp3 up-regulated human monoamine oxidase (MAO) B expression during Caco-2 differentiation. The Journal of biological chemistry 48 12855685
2022 Roseburia intestinalis and Its Metabolite Butyrate Inhibit Colitis and Upregulate TLR5 through the SP3 Signaling Pathway. Nutrients 47 35893896
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
2021 SP3 Protocol for Proteomic Plant Sample Preparation Prior LC-MS/MS. Frontiers in plant science 44 33777071
2003 E2F and Sp1/Sp3 Synergize but are not sufficient to activate the MYCN gene in neuroblastomas. The Journal of biological chemistry 44 14645238
2005 Sp1/Sp3-dependent regulation of human telomerase reverse transcriptase promoter activity by the bioactive sphingolipid ceramide. The Journal of biological chemistry 43 15951564
2001 Regulation of human monoamine oxidase B gene by Sp1 and Sp3. Molecular pharmacology 42 11259630
2001 Sp1- and Sp3-mediated transcriptional regulation of the fibroblast growth factor receptor 1 gene in chicken skeletal muscle cells. The Journal of biological chemistry 42 11756440
2007 Transcription factor Sp3 knockout mice display serious cardiac malformations. Molecular and cellular biology 41 17923686
2006 Sp1 and Sp3 mediate constitutive transcription of the human hyaluronan synthase 2 gene. The Journal of biological chemistry 41 16603733
2004 Sp1 and Sp3 transcription factors mediate trichostatin A-induced and basal expression of extracellular superoxide dismutase. Free radical biology & medicine 41 15451065
2003 Impaired hematopoiesis in mice lacking the transcription factor Sp3. Blood 39 12676787
2023 Angiotensin-converting enzyme inhibitor promotes angiogenesis through Sp1/Sp3-mediated inhibition of notch signaling in male mice. Nature communications 38 36759621
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
2013 Transcription factors Sp1 and Sp3 regulate expression of human ABCG2 gene and chemoresistance phenotype. Molecules and cells 36 23996530
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
2013 Interactions between NF-κB and SP3 connect inflammatory signaling with reduced FGF-10 expression. The Journal of biological chemistry 35 23558680
2005 Regulation of the expression of peptidylarginine deiminase type II gene (PADI2) in human keratinocytes involves Sp1 and Sp3 transcription factors. The Journal of investigative dermatology 35 15854045
1999 The human luteinizing hormone receptor gene promoter: activation by Sp1 and Sp3 and inhibitory regulation. Biochemical and biophysical research communications 34 10491299
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 33 16456404
2003 The PKR kinase promoter binds both Sp1 and Sp3, but only Sp3 functions as part of the interferon-inducible complex with ISGF-3 proteins. Virology 33 12954221
2022 SP3-Enabled Rapid and High Coverage Chemoproteomic Identification of Cell-State-Dependent Redox-Sensitive Cysteines. Molecular & cellular proteomics : MCP 32 35219905
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
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
2016 Physiological TLR5 expression in the intestine is regulated by differential DNA binding of Sp1/Sp3 through simultaneous Sp1 dephosphorylation and Sp3 phosphorylation by two different PKC isoforms. Nucleic acids research 30 27060138
2012 Predictive value of Sp1/Sp3/FLIP signature for prostate cancer recurrence. PloS one 30 23028678
2005 Sumoylation of internally initiated Sp3 isoforms regulates transcriptional repression via a Trichostatin A-insensitive mechanism. Cellular signalling 29 15494207
2002 Role of Sp1 and Sp3 in the nutrient-regulated expression of the human asparagine synthetase gene. The Journal of biological chemistry 29 11867623
2007 Sp1 and Sp3 regulate basal transcription of the human APOBEC3G gene. Nucleic acids research 28 17517765
2007 Sp3 and sp4 transcription factor levels are increased in brains of patients with Alzheimer's disease. Neuro-degenerative diseases 28 17934324
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
2019 Robust hematopoietic specification requires the ubiquitous Sp1 and Sp3 transcription factors. Epigenetics & chromatin 26 31164147
2008 Cell confluency-induced Stat3 activation regulates NHE3 expression by recruiting Sp1 and Sp3 to the proximal NHE3 promoter region during epithelial dome formation. American journal of physiology. Cell physiology 26 19064501
2006 Regulation of neurotrophin-3 gene transcription by Sp3 and Sp4 in neurons. Journal of neurochemistry 26 17059557
2020 ZEB1 Mediates Fibrosis in Corneal Endothelial Mesenchymal Transition Through SP1 and SP3. Investigative ophthalmology & visual science 25 32721022
2024 Ratiometric fluorescent sensing of pyrophosphate with sp³-functionalized single-walled carbon nanotubes. Nature communications 24 38267487
2019 Multiplexed proteome profiling of carbon source perturbations in two yeast species with SL-SP3-TMT. Journal of proteomics 23 31626996
2009 Genistein inhibition of topoisomerase IIalpha expression participated by Sp1 and Sp3 in HeLa cell. International journal of molecular sciences 23 19742137
2000 MRG1 expression in fibroblasts is regulated by Sp1/Sp3 and an Ets transcription factor. The Journal of biological chemistry 23 11114295
2010 Human glycolipid transfer protein gene (GLTP) expression is regulated by Sp1 and Sp3: involvement of the bioactive sphingolipid ceramide. The Journal of biological chemistry 22 20974858
2002 Sp1 and Sp3 activate the rat connexin40 proximal promoter. Biochemical and biophysical research communications 22 11890673
2023 Menstrual blood-derived stem cells exosomal miR-let-7 to ameliorate pulmonary fibrosis through inhibiting ferroptosis by Sp3/HDAC2/Nrf2 signaling pathway. International immunopharmacology 21 38056200
2005 Sp1 and Sp3 transcription factors upregulate the proximal promoter of the human prostate-specific antigen gene in prostate cancer cells. Archives of biochemistry and biophysics 21 15708372
2003 AML-1, PU.1, and Sp3 regulate expression of human bactericidal/permeability-increasing protein. Biochemical and biophysical research communications 21 14623259
1999 Transcriptional regulation of fatty acid synthase gene and ATP citrate-lyase gene by Sp1 and Sp3 in rat hepatocytes(1). FEBS letters 21 10618488
2008 Expression patterns of SP1 and SP3 during mouse spermatogenesis: SP1 down-regulation correlates with two successive promoter changes and translationally compromised transcripts. Biology of reproduction 19 18417714

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