Affinage

USF1

Upstream stimulatory factor 1 · UniProt P22415

Length
310 aa
Mass
33.5 kDa
Annotated
2026-06-10
100 papers in source corpus 43 papers cited in narrative 43 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

USF1 is a ubiquitous basic helix-loop-helix-leucine zipper transcription factor that binds E-box (CANNTG) elements as USF1 homodimers or USF1/USF2 heterodimers to activate or repress a broad spectrum of target genes across metabolism, stress responses, development, and immunity (PMID:7499393, PMID:15242350). Its specificity is achieved largely through combinatorial protein-protein cooperation at composite promoters: USF1 synergizes with TFII-I at Inr/E-box elements (PMID:9384587), with Stat1 at the CIITA GAS/E-box module during IFNγ signaling (PMID:9491997), with Ets-1 at the HIV-1 LTR (PMID:9501094), and with NF-Y, Sp1, ERα, and Pea3 at other loci (PMID:12791656, PMID:15111769, PMID:15466854), while also acting as a repressor that competes with the AhR/Arnt complex at the CYP1A1 XRE (PMID:9374477) and with CLOCK:BMAL1 at circadian E-boxes (PMID:23580255). USF1 nucleates chromatin-modifying activity, recruiting PRMT1/PCAF/SRC-1 to establish active histone marks and barrier function at the β-globin insulator (PMID:17846119) and the hSET1A H3K4 methyltransferase complex to developmental loci such as HoxB4 to license differentiation (PMID:23754954). USF1 activity is extensively tuned by post-translational modification: p38 phosphorylates Thr-153 in response to UV/oxidative stress, which both activates USF1 and primes a downstream acetylation event that redirects its target-gene output away from pigmentation and cell-cycle genes (PMID:11532965, PMID:19389701); cyclin-CDK complexes, PKC, PKA, and AKT enhance its DNA binding (PMID:10548544, PMID:12063293, PMID:30183375); CK2 phosphorylates Thr-100 to suppress USF1/USF2 heterodimerization in a promoter-selective manner (PMID:25194820); and PTP4A1 dephosphorylates Ser-309 to boost its transcriptional activity (PMID:36534975). Beyond transcription, USF1 stabilizes p53 through a non-transcriptional mechanism, physically blocking MDM2-mediated degradation (PMID:24831529). At the physiological level, USF1 regulates lipogenic (FAS) and nutrient-responsive gene expression (PMID:7499393, PMID:24511897), negatively controls brown adipose thermogenesis (PMID:26819196), drives UV-induced nucleotide excision repair gene expression (PMID:22291606), maintains spermatogonial stem cell quiescence (PMID:30759202), and sustains macrophage phagocytosis and chemotaxis (PMID:38578825).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1995 High

    Established USF1 as a physiological E-box-binding regulator of a metabolic gene, showing its protein level itself is nutritionally regulated rather than constant.

    Evidence UV cross-linking, antibody supershift, and immunoblotting at the FAS insulin response sequence across fasted/refed rat liver

    PMID:7499393

    Open questions at the time
    • Mechanism linking nutritional state to USF1 protein abundance not defined
    • Identity/relevance of the 17 kDa USF1-related fasted-state protein unresolved
  2. 1997 High

    Showed USF1 does not act alone but synergizes with a partner factor (TFII-I) at composite Inr/E-box promoters, introducing the combinatorial-cooperation theme.

    Evidence cDNA cloning, in vivo transcription assays, and domain deletion mapping on the adenovirus major late promoter

    PMID:9384587

    Open questions at the time
    • Structural basis of the USF1-TFII-I contact not resolved
    • Generality across cellular promoters not established at the time
  3. 1998 High

    Defined USF1 as a cooperative DNA-binding partner whose recruitment of Stat1 to an adjacent GAS site couples IFNγ signaling to CIITA induction, and established direct DBD-DBD contacts with Ets-1 as a transactivation requirement.

    Evidence EMSA cooperative binding, promoter mutagenesis, reporter assays (CIITA PIV); yeast one-hybrid, Co-IP, dominant-negative analysis (Ets-1/HIV-1 LTR)

    PMID:9491997 PMID:9501094

    Open questions at the time
    • Whether the same surfaces mediate all USF1 partner interactions unknown
    • Stoichiometry of multiprotein complexes on composite promoters not determined
  4. 1999 High

    Identified phosphorylation as a direct switch on USF1 DNA-binding affinity, mapping cyclin-CDK-responsive sites to the USF-specific region outside the DBD.

    Evidence In vitro kinase assays with cyclin A2/B1-p34(cdc2), EMSA, and deletion mutagenesis of recombinant USF1

    PMID:10548544

    Open questions at the time
    • Exact phospho-residues within 143-197 not pinpointed
    • In vivo cell-cycle relevance not demonstrated
  5. 2001 High

    Connected stress signaling to USF1 by showing p38 directly phosphorylates and activates it, making USF1 the effector of UV-induced pigmentation gene activation.

    Evidence In vitro kinase assay, reporter assays, and USF1-/- mouse melanocytes under UV irradiation; parallel demonstration of zinc-responsive MT-I cooperation with MTF-1 in null embryos

    PMID:11230134 PMID:11532965

    Open questions at the time
    • Phosphorylation site not yet mapped at this stage
    • How p38-USF1 selects pigmentation targets unresolved
  6. 2004 High

    Extended the p38-USF1 stress axis to the melanocortin pathway (POMC, MC1R) using loss-of-function genetics, establishing USF1 as a node coordinating the UV photoprotective response.

    Evidence USF1-/- mouse melanocytes, UV irradiation, reporter assays, and RT-PCR

    PMID:15358786

    Open questions at the time
    • Direct vs indirect occupancy at POMC/MC1R E-boxes not fully delineated
    • Crosstalk with other UV-responsive factors unaddressed
  7. 2007 High

    Revealed USF1 as a recruiter of histone-modifying machinery, directly binding PRMT1 and assembling a PCAF/SRC-1 complex that maintains insulator barrier function.

    Evidence Co-IP, ChIP, siRNA knockdown, and dominant-negative peptide interference at the β-globin insulator

    PMID:17846119

    Open questions at the time
    • Order of complex assembly on chromatin not established
    • Whether PRMT1 recruitment generalizes beyond the insulator unknown
  8. 2009 High

    Resolved the p38-USF1 mechanism by mapping Thr-153 phosphorylation as the prerequisite for stress-induced acetylation that redirects USF1 target specificity while preserving nuclear DNA binding.

    Evidence In vitro kinase assay, phospho-specific antibodies, T153A mutagenesis, acetylation and reporter assays

    PMID:19389701

    Open questions at the time
    • Acetyltransferase and acetylated lysine(s) not identified
    • Genome-wide consequences of the phospho-acetyl switch not mapped
  9. 2013 High

    Established two distinct chromatin/developmental roles: USF1 recruits hSET1A for H3K4me3 to license ESC differentiation, and competes with CLOCK:BMAL1 for E-boxes to modulate circadian behavior.

    Evidence ChIP, Co-IP, siRNA, dominant-negative, ESC differentiation assays (HoxB4); genetic suppressor mapping, saturation binding, and genome-wide ChIP (circadian)

    PMID:23580255 PMID:23754954

    Open questions at the time
    • How USF1 vs CLOCK:BMAL1 occupancy is balanced in normal physiology unclear
    • Determinants of USF1-hSET1A locus selectivity unknown
  10. 2014 High

    Uncovered a non-transcriptional function: USF1 stabilizes p53 by blocking MDM2 binding, decoupling a transcription factor from its DNA-binding activity.

    Evidence Co-IP, USF1-/- and USF1-deficient melanoma cells, DBD/transactivation-less truncation rescue, Nutlin-3 controls

    PMID:24831529

    Open questions at the time
    • Structural basis of USF1-p53/MDM2 interplay not defined
    • Stoichiometry and subcellular site of the protective complex unknown
  11. 2014 High

    Defined CK2 phosphorylation of Thr-100 as a dimerization switch that selectively gates USF1 output at metabolic (glucokinase, FAS) versus stress (HO-1) promoters.

    Evidence In vitro kinase, point mutagenesis, Co-IP for USF1-USF2 dimerization, reporter assays with CK2 inhibitors

    PMID:25194820

    Open questions at the time
    • How loss of heterodimerization yields promoter-specific outcomes mechanistically unresolved
    • In vivo CK2-USF1 axis not tested
  12. 2016 High

    Placed USF1 at the center of energy metabolism, showing it negatively regulates brown adipose thermogenesis and positively drives adipogenic FAS expression.

    Evidence USF1-/- mice, BAT sympathectomy, diet-induced obesity, siRNA in brown adipocytes, LPL assays (BAT); ChIP, siRNA, overexpression in adipogenesis (FAS)

    PMID:24511897 PMID:26819196

    Open questions at the time
    • Direct BAT target genes of USF1 not enumerated
    • Reconciliation of pro-adipogenic vs anti-thermogenic roles incomplete
  13. 2019 Medium

    Demonstrated pathogen subversion of USF1 and a stem-cell maintenance role: H. pylori delocalizes USF1/p53 to drive p53 degradation and gastric carcinogenesis, while USF1 maintains spermatogonial stem cell quiescence.

    Evidence Immunofluorescence, Co-IP, USF1-/- mice, H. pylori infection (gastric); USF1-/- mice with histology and SSC marker staining (testis)

    PMID:30759202 PMID:31822580

    Open questions at the time
    • H. pylori factor and signaling that relocalize USF1 not identified
    • Direct USF1 targets governing SSC quiescence unknown
  14. 2023 Medium

    Identified PTP4A1-mediated Ser-309 dephosphorylation as an activating modification driving anti-inflammatory transcription (TNFAIP3/A20) and NF-κB suppression in endothelium.

    Evidence ChIP, luciferase reporter, Co-IP, phospho-site analysis in HUVECs and Ptp4a1 KO/transgenic mice

    PMID:36534975

    Open questions at the time
    • Kinase that phosphorylates S309 in this context not identified
    • Single lab; reciprocal validation of PTP4A1-USF1 axis limited
  15. 2024 Medium

    Extended USF1 into vascular disease and immune aging, driving USP14-dependent NLRC5 stabilization in atherosclerotic EndMT and sustaining macrophage phagocytosis and chemotaxis.

    Evidence ChIP, dual-luciferase, Co-IP, ApoE-/- mice (USP14/NLRC5/EndMT); siRNA in human monocyte-derived macrophages with functional and transcriptomic readouts

    PMID:38424494 PMID:38578825

    Open questions at the time
    • Direct vs indirect control of the actin/morphology program in macrophages unresolved
    • Single-lab findings without independent replication

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the layered post-translational code (p38/Thr-153, CK2/Thr-100, AKT, CDK, PTP4A1/Ser-309) is integrated to select among the hundreds of E-box targets in a given cell remains unresolved.
  • No unified model linking specific modifications to genome-wide target selection
  • Structural basis of partner-dependent specificity uncharacterized
  • Endogenous full-length occupancy maps across modification states lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 5 GO:0140110 transcription regulator activity 5 GO:0140097 catalytic activity, acting on DNA 2
Localization
GO:0005634 nucleus 4
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-4839726 Chromatin organization 2 R-HSA-73894 DNA Repair 1 R-HSA-9909396 Circadian clock 1
Partners
ETS-1NF-YP53PDX-1PRMT1STAT1TFII-IUSF2

Evidence

Reading pass · 43 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 USF-1 binds cooperatively with Stat1 to an adjacent GAS/E-box motif on the CIITA promoter IV (PIV) to activate CIITA transcription in response to IFNγ; both Stat1 and USF-1 are essential, and Stat1 only binds the GAS site in the presence of USF-1 at the E box. Electrophoretic mobility shift assay (EMSA), cooperative binding assays, functional promoter deletion/mutagenesis, transfection reporter assays Immunity High 9491997
1997 TFII-I (a 120 kDa transcription factor) interacts physically and functionally with USF1; TFII-I stimulates USF1 binding to both Inr and E-box elements and the two proteins act synergistically to activate transcription through both elements of the adenovirus major late promoter in vivo. Domains of USF1 required for independent and synergistic activation functions were identified. cDNA cloning, ectopic expression, in vivo transcription assays, domain deletion analysis, cooperative DNA-binding assays The EMBO journal High 9384587
2001 USF-1 is phosphorylated and activated by the stress-responsive p38 kinase; this modification is required for UV-induced activation of the Tyrosinase promoter in pigment cells, while Mitf regulates basal Tyrosinase expression. In vitro kinase assay, reporter gene assays, USF-1 −/− mouse melanocytes, UV irradiation model The EMBO journal High 11532965
2004 UV-induced activation of the POMC and MC1R promoters is mediated by p38 stress-activated kinase signaling to USF-1; melanocytes from USF-1 −/− mice fail to up-regulate POMC and MC1R in response to UV irradiation. Loss-of-function mouse model (USF-1 −/−), reporter gene assays, UV irradiation, RT-PCR The Journal of biological chemistry High 15358786
2009 USF-1 is phosphorylated on Thr-153 by p38 in response to UV/DNA damage/oxidative stress, and this phosphorylation is a prerequisite for subsequent acetylation of USF-1; phospho-acetylated USF-1 is nuclear, binds DNA, but displays altered (reduced) transcriptional activation toward pigmentation and cell-cycle genes. In vitro kinase assay, phospho-specific antibodies, acetylation assays, mutagenesis (T153A), reporter gene assays, nuclear localization studies The Journal of biological chemistry High 19389701
2007 USF1 recruits histone modification complexes to the β-globin locus insulator: USF1 interacts directly with histone H4R3-specific methyltransferase PRMT1, and together with PCAF and SRC-1 forms a complex with both HMT and HAT activities. siRNA knockdown of USF1 causes localized loss of H4R3 methylation and other euchromatin marks at the insulator; a dominant-negative USF1 peptide abolishes insulator barrier function. Co-immunoprecipitation, chromatin immunoprecipitation, siRNA knockdown, dominant-negative peptide interference, histone modification assays Molecular and cellular biology High 17846119
1998 USF-1 directly interacts with Ets-1 through their respective DNA-binding domains; the USF-1/Ets-1 complex binds adjacent E-box and Ets sites on the HIV-1 LTR enhancer and the two factors synergize for transactivation. A dominant-negative Ets-1 that lacks DNA binding but retains the USF-1 interaction surface inhibits USF-1-mediated transactivation, demonstrating the importance of direct protein–protein contact. Yeast one-hybrid screen, Co-immunoprecipitation, EMSA, reporter gene assays, dominant-negative mutant analysis, domain mapping The EMBO journal High 9501094
1995 USF1 and USF2 are the major proteins binding the E-box-containing insulin response sequence (IRS) of the fatty acid synthase (FAS) promoter; the amount of the 43 kDa USF1 protein is dramatically increased in liver of refed rats, while a 17 kDa USF1-related protein is high in fasted rats and decreases upon refeeding, indicating nutritional regulation of USF1 expression. Competition gel-shift assay, antibody supershift, UV cross-linking, immunoblotting of fasted/refed rat liver The Journal of biological chemistry High 7499393
1999 The DNA-binding affinity of recombinant USF-1 is greatly increased by phosphorylation with cyclin A2-p34(cdc2) or cyclin B1-p34(cdc2) complexes; the phosphorylation site(s) map to amino acids 143–197, outside the minimal DNA-binding domain but within the USF-specific region, and deletion studies show this region regulates DNA binding in a phosphorylation-dependent manner. In vitro kinase assay with cyclin–CDK complexes, recombinant USF-1, EMSA, deletion mutagenesis The Biochemical journal High 10548544
2013 USF1 competes with the CLOCK:BMAL1 complex for E-box sites in circadian target genes; a SNP in the Usf1 promoter elevates Usf1 transcript and protein, increasing USF1 occupancy genome-wide and suppressing the ClockΔ19 behavioral phenotype. Saturation binding experiments show reduced affinity of the CLOCKΔ19:BMAL1 complex for E-box sites, permitting this increased USF1 occupancy. Genetic mapping, quantitative saturation binding, genome-wide ChIP, promoter-SNP analysis, behavioral circadian assays in mice eLife High 23580255
2014 USF1 stabilizes the p53 protein by preventing p53-MDM2 complex formation and MDM2-mediated degradation of p53; in USF1-deficient cells, MDM2–p53 interaction is enhanced and p53 levels drop. A USF1 truncated protein lacking DNA-binding and transactivation domains can still restore p53 induction, indicating a non-transcriptional mechanism of USF1 in p53 stabilization. Co-immunoprecipitation (p53/MDM2), Usf1 −/− mouse and USF1-deficient melanoma cells, dominant-negative and truncation constructs, Nutlin-3 rescue, Western blotting PLoS genetics High 24831529
2019 H. pylori delocalizes USF1 into cytoplasmic foci near cell membranes, prevents USF1/p53 nuclear complex formation, and relocates USF1/p53 complexes to the cytoplasm, thereby impairing their transcriptional function and promoting proteasomal degradation of p53; Usf1 −/− mice show accelerated gastric carcinogenesis. Immunofluorescence localization, co-immunoprecipitation (USF1/p53), Usf1 −/− mouse model, H. pylori infection of gastric cell lines, camptothecin DNA-damage model Gut High 31822580
2013 USF1 recruits the hSET1A histone H3K4 methyltransferase complex to the HoxB4 promoter, governing H3K4me3 deposition and transcriptional preinitiation complex assembly; dominant-negative AUSF1 or siRNA knockdown of hSET1A reduces mesoderm markers and inhibits lineage differentiation from ESCs. ChIP, Co-immunoprecipitation, siRNA knockdown, dominant-negative overexpression, ESC differentiation assays PLoS genetics High 23754954
2001 USF1 cooperates with MTF-1 to activate the metallothionein-I (MT-I) gene in visceral endoderm cells in response to zinc; USF1 binds an E-box1 element at -223 bp in the MT-I promoter and is required for optimal (but not basal) zinc-responsive MT-I expression, as shown by embryo genetics and promoter binding. MTF-1 and USF1 null mouse embryo genetics, EMSA, promoter mutagenesis, maternal zinc manipulation The EMBO journal High 11230134
2016 USF1 deficiency in mice activates brown adipose tissue (BAT) thermogenesis, increases energy expenditure, and directs triglycerides from circulation to BAT via a lipoprotein lipase-dependent mechanism. In brown adipocytes, Usf1 silencing amplifies adrenergic response, indicating a direct negative regulatory role of USF1 in BAT activation. Usf1 −/− mice, BAT sympathectomy, diet-induced obesity model, siRNA silencing in brown adipocytes, adrenergic stimulation assays, lipoprotein lipase activity measurements Science translational medicine High 26819196
2014 CK2 phosphorylates USF1 on Thr-100 (identified by deletion and point mutagenesis); CK2 phosphorylation of USF1 inhibits USF1-USF2 heterodimerization, and inhibition of CK2 stimulates transcription from glucokinase and FAS promoters but not HO-1 promoter, demonstrating promoter-specific regulation by CK2-mediated USF1 phosphorylation. In vitro kinase assay, deletion and point mutants, co-immunoprecipitation (USF1-USF2 interaction), reporter gene assays, CK2 inhibitors Cellular signalling High 25194820
2017 CK2 phosphorylates USF1 and strengthens USF1-PDX-1 interaction; USF1 transrepresses the PDX-1 promoter in a CK2-dependent manner, and this repression is abrogated by elevated glucose or CK2 inhibition. A phospho-mutant of USF1 reduces PDX-1 promoter binding, indicating that CK2-mediated USF1 phosphorylation modulates both PDX-1 transcription and USF1-PDX-1 protein interaction. Promoter luciferase assays, Co-immunoprecipitation (USF1-PDX-1), CK2 inhibitor treatment, USF1 phospho-mutant, primary islet insulin secretion assay Scientific reports Medium 29180680
2002 USF1 and USF2 trans-repress the iNOS gene in mesangial cells by binding an E-box at -893/-888; mutation of this E-box augments IL-1β-induced iNOS promoter activity. Cotransfection of USF-1 and USF-2 suppresses IL-1β-stimulated iNOS promoter activity, and dominant-negative USF-2 or cis-element decoys augment it. Site-directed mutagenesis of iNOS promoter E-box, EMSA, antibody supershift, cotransfection reporter assays, dominant-negative USF-2 constructs American journal of physiology. Cell physiology High 12225970
2002 USF1 binds the PAI-1 proximal promoter E-box (CACGTG at -160 to -165) in a growth-state-dependent manner; phosphorylated USF1 (isolated by promoter-DNA affinity chromatography) is the predominant E-box-binding form in wound-stimulated cells. Wounding induces USF1 nuclear accumulation and E-box binding within 2 h, correlating with PAI-1 transcriptional induction. EMSA, UV cross-linking, deoxyoligonucleotide affinity chromatography, immunocytochemistry, Western blotting, in vitro wound model Journal of cell science Medium 12235287
2002 Purified rat USF1 is phosphorylated in vitro by PKC and PKA (but not casein kinase II); phosphorylated USF1 by either kinase shows increased DNA-binding activity to the cardiac α-MHC HME E-box, and PKC phosphorylation additionally promotes USF1 multimer formation. In vivo, USF1 is found in at least two phosphorylated forms in ventricular myocytes. In vitro kinase assay (PKC, PKA, CK2), EMSA, 2D gel electrophoresis of in vivo phosphorylated nuclear proteins American journal of physiology. Heart and circulatory physiology High 12063293
2003 A USF1/USF2 heterodimer binds a CAGCTG (E-box) element in the first intron of the FcεRI α-chain gene and activates its expression; overexpression of antisense USF2 represses FcεRI α-chain promoter activity and decreases α-chain mRNA in mast cell lines. EMSA with antibodies and in vitro-translated proteins, cotransfection reporter assays, antisense USF2 knockdown European journal of immunology Medium 11180124
2000 USF1 and USF2 bind the HOXB4 promoter E-box (HXRE-2) in vitro and in K562 cells; cotransfection assays show USF-1 and USF-2 (but not MITF) induce the HOXB4 promoter in K562 and CD34+ cells via MAPK pathway activation. Yeast one-hybrid screen, EMSA, cotransfection reporter assays in K562 and CD34+ cells, HXRE-2 mutagenesis The Journal of experimental medicine Medium 11085749
2003 NF-Y and USF1/2 interact biochemically on the HOXB4 promoter (identified by Co-IP), and the NF-Y/USF1/2 complex is required for full HOXB4 promoter activity in hematopoietic cells; ChIP shows reduced NF-Y occupancy in more differentiated granulocytic cells consistent with lower HOXB4 expression. Co-immunoprecipitation (NF-Y/USF1-2 interaction), ChIP, cotransfection reporter assays, E-box mutagenesis Blood Medium 12791656
2007 v-Src down-regulates the SSeCKS/AKAP12 alpha promoter by recruiting HDAC1 into a USF1-Sp1-Sp3 complex; v-Src does not alter USF1 binding to the E-box but increases Sp1/Sp3 binding. HDAC1 recruitment is necessary and sufficient for promoter repression; TSA (HDAC inhibitor) restores SSeCKS levels. Promoter deletion analysis, chromatin immunoprecipitation, cotransfection reporter assays, TSA and 5-azacytidine treatment, protein expression analysis The Journal of biological chemistry Medium 17626016
2011 USF1 is required for TGF-β1 and renin gene expression in diabetic kidney disease; high glucose inhibits AMPK activity and increases USF1 nuclear translocation in mesangial cells. Activation of AMPK with AICAR stimulates AMPK and reduces nuclear USF1 accumulation, indicating AMPK regulates USF1 nuclear localization. USF1 −/− mice crossed with Akita diabetic mice, mesangial cell culture, AMPK activation with AICAR, nuclear fractionation, Western blotting American journal of physiology. Renal physiology Medium 21543418
2011 USF1 is activated downstream of PI3K/Akt/GSK3 signaling; GSK3 phosphorylates USF1 on the previously described activating site Thr-153 as well as on a newly identified site Ser-186. USF1 (together with MITF) drives transcription of proapoptotic and cell-cycle arrest genes when PI3K is inhibited, coordinately with FoxO. ChIP, siRNA knockdown, pharmacological PI3K inhibition, identification of GSK3 phosphorylation sites on USF1, gene expression profiling The Journal of biological chemistry Medium 21873430
2008 Retinoic acid triggers a feed-forward loop in which CREB (activated directly by PKA) induces USF1 expression, and the induced USF1 then binds the MKP1 promoter E-box to drive the late phase of MKP1 transcription; both CREB and USF1 binding to the MKP1 promoter were confirmed by ChIP. ChIP (CREB and USF1 binding to MKP1 promoter), gel-shift assay, siRNA knockdown of CREB and USF1, MKP1 promoter reporter with CRE/E-box mutations Molecular and cellular biology Medium 18625721
2003 H. pylori activates COX-2 gene transcription via a proximal CRE/E-box element at -56 to -48 in the cox-2 promoter; USF1/2 and CREB transcription factors binding to this element transmit H. pylori-dependent COX-2 transcription, and this is mediated by MEK/ERK1/2 signaling activated by bacterial virulence factors outside the cagPAI. Promoter deletion analysis, EMSA (USF1/2 and CREB binding), MEK/ERK inhibitor experiments, reporter assays, mRNA/protein quantification Cellular microbiology Medium 14531897
2004 USF-1 and ERα form a multi-protein complex with Sp1 at the ERα minimal promoter; Sp1 and USF-1 bind directly to the promoter (shown by EMSA), while ERα interacts with USF-1 in vitro (GST pull-down) without directly binding DNA, and combined overexpression causes synergistic transactivation. EMSA, GST pull-down, cotransfection reporter assays Breast cancer research and treatment Medium 15111769
2004 USF1 and USF2 constitutively bind an E-box in the proximal promoter of the human HO-1 gene in vivo (confirmed by ChIP and DMS footprinting); overexpression of USF1 or USF2 enhances basal HO-1 expression, and a dominant-negative USF reduces it, showing USFs are required for high-level HO-1 expression. ChIP, DMS in vivo footprinting, EMSA, dominant-negative USF overexpression, reporter assays The Biochemical journal High 15242350
2012 USF-1 up-regulates CSA and HR23A gene expression in response to UV irradiation, which are key players in TCR and GGR sub-pathways of nucleotide excision repair, through a p53-independent mechanism; Usf1 −/− mice show compromised UV-induced DNA repair. In vitro and in vivo UV irradiation assays, Usf1 −/− mouse model, mRNA quantification, NER activity assays PLoS genetics Medium 22291606
2003 A novel alternative splicing isoform of USF1, termed USF1/BD, lacks the N-terminal transactivation domain; it localizes to the nucleus, retains DNA-binding activity as both homodimer and heterodimer with wild-type USF1, and represses the angiotensinogen gene promoter when transfected into cells. cDNA cloning, nuclear localization assay (ectopic expression), in vitro translation DNA-binding assay, reporter gene assay International journal of molecular medicine Medium 12851711
1997 USF1 suppresses CYP1A1 induction by competing with the AhR·Arnt complex for binding to the XRE, which overlaps with a USF1 E-box binding site; transfection of USF1 into HepG2 cells prevents AhR·Arnt–XRE interaction and depresses MC-induced CYP1A1 mRNA induction. EMSA, antibody supershift, XRE-TK/Luc reporter cotransfection, S1 nuclease protection assay The Journal of biological chemistry Medium 9374477
2004 Pea3 cooperates with USF-1 for transactivation of the bax promoter without directly binding DNA; E-boxes in the minimal bax promoter are required for Pea3 transactivation potential, and USF-1 can form a ternary complex with Pea3 and DNA (shown by antibody-mediated EMSA supershift). Pea3 overexpression and siRNA, reporter gene assays, EMSA with antibody supershift demonstrating ternary complex The Journal of biological chemistry Medium 15466854
2019 USF1 is required for maintenance of spermatogonial stem cells (SSCs) in mice; Usf1 −/− mice show SSC over-proliferation and age-dependent depletion of SSCs leading to progressive spermatogenic decline, testicular atrophy, and reduced sperm production, demonstrating a direct role in maintaining SSC quiescence. Usf1 −/− mouse model, histology, immunostaining for SSC and Sertoli markers, spermatogenesis assessment Endocrinology Medium 30759202
2016 USF1 (and USF2) binding to the FAS gene E-box promoter element drives FAS transcription in adipocytes; knockdown of USF1 represses adipogenesis along with decreased FAS expression, while USF1 overexpression enhances adipogenesis and FAS expression; valproic acid suppresses adipogenesis partly by down-regulating USF1. ChIP (USF1 binding to FAS promoter E-box), siRNA knockdown, overexpression, luciferase reporter assay, adipogenesis quantification The Biochemical journal Medium 24511897
2018 AKT phosphorylates USF-1 in response to insulin/PI3K signaling, enhancing USF-1 binding to the WBP2 promoter E-box and increasing WBP2 transcription; this was identified by yeast one-hybrid, confirmed by ChIP and tandem mass spectrometry, and the phosphorylation-dependent E-box binding demonstrated by reporter assay. Yeast one-hybrid, ChIP, tandem mass spectrometry (phosphorylation site), luciferase reporter with E-box mutation, AKT inhibitor treatment FASEB journal Medium 30183375
2023 PTP4A1 increases the transcriptional activity of USF1 by dephosphorylating its S309 residue, which in turn drives transcription of TNFAIP3/A20 and thereby inhibits NF-κB activity and vascular inflammation; shown by ChIP, luciferase reporter, and Co-IP assays. ChIP, luciferase reporter, Co-IP, siRNA and overexpression in HUVECs, Ptp4a1 KO and transgenic mice, phospho-site specific analysis Cardiovascular research Medium 36534975
2024 USF1 transcriptionally activates USP14 by binding its promoter (confirmed by ChIP and dual-luciferase assay), which promotes deubiquitination and stabilization of NLRC5, leading to Smad2/3 pathway activation and endothelial-to-mesenchymal transition (EndMT) driving atherosclerosis. Dual-luciferase reporter, ChIP, Co-IP (USP14/NLRC5), siRNA knockdown, ApoE −/− mouse atherosclerosis model Molecular medicine Medium 38424494
2016 Inhibition of HDAC2/3 by apicidin increases USF1 acetylation, enhances USF1 association with HDAC2/3 and with the ADAM10 promoter, and up-regulates ADAM10 expression via an ERK-dependent mechanism; USF1 knockdown prevents apicidin-induced ADAM10 up-regulation. Luciferase reporter assay, USF1 knockdown (siRNA), USF1 acetylation assay, Co-immunoprecipitation (USF1/HDAC2/3), ChIP, ERK inhibitor (U0126) FASEB journal Medium 28003340
2009 The rs1867277 A allele in the FOXE1 5' UTR recruits USF1/USF2 as a complex (demonstrated by DNA-binding assays); only the A allele (not the G allele) forms a USF1/USF2 complex, leading to allele-dependent transcriptional regulation of FOXE1. DNA-binding (EMSA/pull-down) assays, allele-specific binding, transfection reporter assays PLoS genetics Medium 19730683
2024 Knockdown of USF1 or MYC in human monocyte-derived macrophages decreases phagocytosis and chemotaxis, increases cell size, alters morphology, and reduces actin content; these phenotypes concordantly reflect the functional decline seen in macrophages from older donors, identifying USF1 as a driver of macrophage age-related functional decline. siRNA knockdown of USF1 in human MDMs, phagocytosis assay, chemotaxis assay, morphology/actin quantification, transcriptomic analysis Cell reports Medium 38578825
2000 USF1 and USF2 are the major transcription factors binding the FMR1 promoter in brain and testis extracts; methylation of the promoter reduces USF1/USF2 binding and abolishes α-Pal/Nrf-1 binding, providing a mechanism by which CpG methylation silences FMR1 transcription beyond histone deacetylase recruitment. EMSA with brain and testis nuclear extracts, antibody supershift, methylation interference, site mutagenesis, reporter gene assays The Journal of biological chemistry Medium 11058604

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Activation of the MHC class II transactivator CIITA by interferon-gamma requires cooperative interaction between Stat1 and USF-1. Immunity 307 9491997
2003 A novel single nucleotide polymorphism within the 5' tandem repeat polymorphism of the thymidylate synthase gene abolishes USF-1 binding and alters transcriptional activity. Cancer research 305 12782596
2004 Familial combined hyperlipidemia is associated with upstream transcription factor 1 (USF1). Nature genetics 242 14991056
1997 Cloning of an inr- and E-box-binding protein, TFII-I, that interacts physically and functionally with USF1. The EMBO journal 175 9384587
2001 The Usf-1 transcription factor is a novel target for the stress-responsive p38 kinase and mediates UV-induced Tyrosinase expression. The EMBO journal 174 11532965
2009 The variant rs1867277 in FOXE1 gene confers thyroid cancer susceptibility through the recruitment of USF1/USF2 transcription factors. PLoS genetics 132 19730683
2009 A systems genetics approach implicates USF1, FADS3, and other causal candidate genes for familial combined hyperlipidemia. PLoS genetics 126 19750004
1998 Cooperative interaction of ets-1 with USF-1 required for HIV-1 enhancer activity in T cells. The EMBO journal 118 9501094
1995 Upstream stimulatory factors bind to insulin response sequence of the fatty acid synthase promoter. USF1 is regulated. The Journal of biological chemistry 104 7499393
2007 USF1 recruits histone modification complexes and is critical for maintenance of a chromatin barrier. Molecular and cellular biology 102 17846119
2004 UV-induced expression of key component of the tanning process, the POMC and MC1R genes, is dependent on the p-38-activated upstream stimulating factor-1 (USF-1). The Journal of biological chemistry 101 15358786
2008 Whole-genome maps of USF1 and USF2 binding and histone H3 acetylation reveal new aspects of promoter structure and candidate genes for common human disorders. Genome research 86 18230803
2001 The transcription factors MTF-1 and USF1 cooperate to regulate mouse metallothionein-I expression in response to the essential metal zinc in visceral endoderm cells during early development. The EMBO journal 83 11230134
2000 Interaction of the transcription factors USF1, USF2, and alpha -Pal/Nrf-1 with the FMR1 promoter. Implications for Fragile X mental retardation syndrome. The Journal of biological chemistry 77 11058604
2019 USF1 defect drives p53 degradation during Helicobacter pylori infection and accelerates gastric carcinogenesis. Gut 74 31822580
2003 Helicobacter pylori stimulates host cyclooxygenase-2 gene transcription: critical importance of MEK/ERK-dependent activation of USF1/-2 and CREB transcription factors. Cellular microbiology 71 14531897
2005 USF1 and dyslipidemias: converging evidence for a functional intronic variant. Human molecular genetics 69 16076849
2019 LncRNA LOXL1-AS1 facilitates the tumorigenesis and stemness of gastric carcinoma via regulation of miR-708-5p/USF1 pathway. Cell proliferation 68 31468594
2013 Usf1, a suppressor of the circadian Clock mutant, reveals the nature of the DNA-binding of the CLOCK:BMAL1 complex in mice. eLife 65 23580255
2004 Variation in USF1 shows haplotype effects, gene : gene and gene : environment associations with glucose and lipid parameters in the European Atherosclerosis Research Study II. Human molecular genetics 65 15175273
2016 USF1 deficiency activates brown adipose tissue and improves cardiometabolic health. Science translational medicine 64 26819196
2003 NF-Y cooperates with USF1/2 to induce the hematopoietic expression of HOXB4. Blood 63 12791656
2013 USF1 and hSET1A mediated epigenetic modifications regulate lineage differentiation and HoxB4 transcription. PLoS genetics 52 23754954
2019 Knockdown of USF1 Inhibits the Vasculogenic Mimicry of Glioma Cells via Stimulating SNHG16/miR-212-3p and linc00667/miR-429 Axis. Molecular therapy. Nucleic acids 51 30743215
2001 Upstream stimulating factor-1 (USF1) and USF2 bind to and activate the promoter of the adenomatous polyposis coli (APC) tumor suppressor gene. Journal of cellular biochemistry 51 11241666
2024 Aging-related defects in macrophage function are driven by MYC and USF1 transcriptional programs. Cell reports 50 38578825
1997 The basic helix-loop-helix-zipper transcription factor USF1 regulates expression of the surfactant protein-A gene. The Journal of biological chemistry 48 9287355
2006 Risk alleles of USF1 gene predict cardiovascular disease of women in two prospective studies. PLoS genetics 46 16699592
1999 DNA-binding activity of the transcription factor upstream stimulatory factor 1 (USF-1) is regulated by cyclin-dependent phosphorylation. The Biochemical journal 45 10548544
2022 Upregulation of Superenhancer-Driven LncRNA FASRL by USF1 Promotes De Novo Fatty Acid Biosynthesis to Exacerbate Hepatocellular Carcinoma. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 44 36307901
2017 The Role of HOTAIR/miR-148b-3p/USF1 on Regulating the Permeability of BTB. Frontiers in molecular neuroscience 43 28701916
2002 Epithelial monolayer wounding stimulates binding of USF-1 to an E-box motif in the plasminogen activator inhibitor type 1 gene. Journal of cell science 43 12235287
2019 USF1-induced upregulation of LINC01048 promotes cell proliferation and apoptosis in cutaneous squamous cell carcinoma by binding to TAF15 to transcriptionally activate YAP1. Cell death & disease 42 30931936
1997 Inhibition of the transcription of CYP1A1 gene by the upstream stimulatory factor 1 in rabbits. Competitive binding of USF1 with AhR.Arnt complex. The Journal of biological chemistry 41 9374477
2018 Suppression of metastasis through inhibition of chitinase 3-like 1 expression by miR-125a-3p-mediated up-regulation of USF1. Theranostics 40 30214629
2009 Target gene specificity of USF-1 is directed via p38-mediated phosphorylation-dependent acetylation. The Journal of biological chemistry 39 19389701
2009 Genetic association and interaction analysis of USF1 and APOA5 on lipid levels and atherosclerosis. Arteriosclerosis, thrombosis, and vascular biology 39 19910639
2000 Hematopoietic expression of HOXB4 is regulated in normal and leukemic stem cells through transcriptional activation of the HOXB4 promoter by upstream stimulating factor (USF)-1 and USF-2. The Journal of experimental medicine 39 11085749
2008 Retinoic acid utilizes CREB and USF1 in a transcriptional feed-forward loop in order to stimulate MKP1 expression in human immunodeficiency virus-infected podocytes. Molecular and cellular biology 38 18625721
2007 Regulation of IL-10 expression by upstream stimulating factor (USF-1) in glioma-associated microglia. Journal of neuroimmunology 36 17289164
2001 Promoter I of the ovine acetyl-CoA carboxylase-alpha gene: an E-box motif at -114 in the proximal promoter binds upstream stimulatory factor (USF)-1 and USF-2 and acts as an insulin-response sequence in differentiating adipocytes. The Biochemical journal 35 11583573
2014 p53 requires the stress sensor USF1 to direct appropriate cell fate decision. PLoS genetics 34 24831529
2007 v-Src-mediated down-regulation of SSeCKS metastasis suppressor gene promoter by the recruitment of HDAC1 into a USF1-Sp1-Sp3 complex. The Journal of biological chemistry 34 17626016
2004 Regulation of the estrogen receptor alpha minimal promoter by Sp1, USF-1 and ERalpha. Breast cancer research and treatment 34 15111769
2011 The E-box binding factors Max/Mnt, MITF, and USF1 act coordinately with FoxO to regulate expression of proapoptotic and cell cycle control genes by phosphatidylinositol 3-kinase/Akt/glycogen synthase kinase 3 signaling. The Journal of biological chemistry 33 21873430
2020 The transcription factor USF1 promotes glioma cell invasion and migration by activating lncRNA HAS2-AS1. Bioscience reports 31 32776110
2004 Upstream stimulatory factors, USF1 and USF2, bind to the human haem oxygenase-1 proximal promoter in vivo and regulate its transcription. The Biochemical journal 31 15242350
1996 Mouse USF1 gene cloning: comparative organization within the c-myc gene family. Mammalian genome : official journal of the International Mammalian Genome Society 30 8875887
2002 Role of USF1 phosphorylation on cardiac alpha-myosin heavy chain promoter activity. American journal of physiology. Heart and circulatory physiology 29 12063293
2011 Role of the USF1 transcription factor in diabetic kidney disease. American journal of physiology. Renal physiology 28 21543418
2005 Role of USF1 and USF2 as potential repressor proteins for human intestinal monocarboxylate transporter 1 promoter. American journal of physiology. Gastrointestinal and liver physiology 28 15691871
2021 miR-210-3p Promotes Lung Cancer Development and Progression by Modulating USF1 and PCGF3. OncoTargets and therapy 26 34140779
2016 Histone deacetylase inhibitor apicidin increases expression of the α-secretase ADAM10 through transcription factor USF1-mediated mechanisms. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 26 28003340
2008 Association analysis of allelic variants of USF1 in coronary atherosclerosis. Arteriosclerosis, thrombosis, and vascular biology 26 18276913
2014 Association of USF1 and APOA5 polymorphisms with familial combined hyperlipidemia in an Italian population. Molecular and cellular probes 25 25308402
2024 USF1 transcriptionally activates USP14 to drive atherosclerosis by promoting EndMT through NLRC5/Smad2/3 axis. Molecular medicine (Cambridge, Mass.) 24 38424494
2019 Transcriptional Regulation Factors of the Human Mitochondrial Aspartate/Glutamate Carrier Gene, Isoform 2 (SLC25A13): USF1 as Basal Factor and FOXA2 as Activator in Liver Cells. International journal of molecular sciences 24 30995827
2005 The roles of Sp1, Sp3, USF1/USF2 and NRF-1 in the regulation and three-dimensional structure of the Fragile X mental retardation gene promoter. The Biochemical journal 24 15479157
2022 USF1/CD90 signaling in maintaining glioblastoma stem cells and tumor-associated macrophages adhesion. Neuro-oncology 23 35287174
2022 USF1-ATRAP-PBX3 Axis Promote Breast Cancer Glycolysis and Malignant Phenotype by Activating AKT/mTOR Signaling. International journal of biological sciences 23 35414770
2007 USF1 gene variants, cardiovascular risk, and mortality in European Americans: analysis of two US cohort studies. Arteriosclerosis, thrombosis, and vascular biology 23 17885212
2004 Pea3 transcription factor cooperates with USF-1 in regulation of the murine bax transcription without binding to an Ets-binding site. The Journal of biological chemistry 23 15466854
2008 Genetic variants in the USF1 gene are associated with low-density lipoprotein cholesterol levels and incident type 2 diabetes mellitus in women: results from the MONICA/KORA Augsburg case-cohort study, 1984-2002. European journal of endocrinology 22 18593823
2020 USF1-induced overexpression of long noncoding RNA WDFY3-AS2 promotes lung adenocarcinoma progression via targeting miR-491-5p/ZNF703 axis. Molecular carcinogenesis 21 32275336
2008 Upstream transcription factor 1 (USF1) in risk of type 2 diabetes: association study in 2000 Dutch Caucasians. Molecular genetics and metabolism 21 18445538
2008 USF1/2 transcription factor DNA-binding activity is induced during rat Sertoli cell differentiation. Biology of reproduction 21 18768914
2004 A promoter polymorphism in the central MHC gene, IKBL, influences the binding of transcription factors USF1 and E47 on disease-associated haplotypes. Gene expression 21 15473256
2005 Common polymorphisms in the USF1 gene are not associated with type 2 diabetes in French Caucasians. Diabetes 20 16186412
2001 A complex composed of USF1 and USF2 activates the human FcepsilonRI alpha chain expression via a CAGCTG element in the first intron. European journal of immunology 19 11180124
2023 Endothelial PTP4A1 mitigates vascular inflammation via USF1/A20 axis-mediated NF-κB inactivation. Cardiovascular research 18 36534975
2014 Upstream Transcription Factor 1 (USF1) allelic variants regulate lipoprotein metabolism in women and USF1 expression in atherosclerotic plaque. Scientific reports 18 24722012
2012 USF-1 is critical for maintaining genome integrity in response to UV-induced DNA photolesions. PLoS genetics 18 22291606
2002 USF-1 and USF-2 trans-repress IL-1beta-induced iNOS transcription in mesangial cells. American journal of physiology. Cell physiology 18 12225970
2000 Growth state-dependent binding of USF-1 to a proximal promoter E box element in the rat plasminogen activator inhibitor type 1 gene. Experimental cell research 18 11010817
2020 USF1-mediated upregulation of lncRNA GAS6-AS2 facilitates osteosarcoma progression through miR-934/BCAT1 axis. Aging 17 32269179
2018 Phosphorylation of E-box binding USF-1 by PI3K/AKT enhances its transcriptional activation of the WBP2 oncogene in breast cancer cells. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 17 30183375
2017 Functional interplay between the transcription factors USF1 and PDX-1 and protein kinase CK2 in pancreatic β-cells. Scientific reports 17 29180680
2007 USF1 gene variants contribute to metabolic traits in men in a longitudinal 32-year follow-up study. Diabetologia 17 18097648
2014 Requirement of the transcription factor USF1 in bovine oocyte and early embryonic development. Reproduction (Cambridge, England) 16 25385722
2012 Upstream transcription factor 1 (USF1) polymorphisms associate with Alzheimer's disease-related neuropathological lesions: Tampere Autopsy Study. Brain pathology (Zurich, Switzerland) 16 22390463
2007 Associations between USF1 gene variants and cardiovascular risk factors in the Quebec Family Study. Clinical genetics 16 17309647
2019 Transcription Factor USF1 Is Required for Maintenance of Germline Stem Cells in Male Mice. Endocrinology 15 30759202
2014 Suppression of adipogenesis by valproic acid through repression of USF1-activated fatty acid synthesis in adipocytes. The Biochemical journal 15 24511897
2003 HOXB7 expression is regulated by the transcription factors NF-Y, YY1, Sp1 and USF-1. Biochimica et biophysica acta 15 12697323
2003 Cloning and characterization of a novel splicing isoform of USF1. International journal of molecular medicine 15 12851711
2020 TUG1 long non-coding RNA enlists the USF1 transcription factor to overexpress ROMO1 leading to hepatocellular carcinoma growth and metastasis. MedComm 14 34766130
2018 USF1 deficiency alleviates inflammation, enhances cholesterol efflux and prevents cholesterol accumulation in macrophages. Lipids in health and disease 14 30545366
2009 Gene-gene interaction between APOA5 and USF1: two candidate genes for the metabolic syndrome. Obesity facts 14 20054229
1997 Characterization of UEF-4, a DNA-binding protein required for transcriptional synergism between two AP-1 sites in the human urokinase enhancer. The Journal of biological chemistry 14 9295342
1997 Upstream stimulatory factor 1 (USF1) suppresses induction of CYP1A1 mRNA by 3-methylcholanthrene (MC) in HepG2 cells. Biochemical and biophysical research communications 14 9388470
2016 USF1 prompt melanoma through upregulating TGF-β signaling pathway. European review for medical and pharmacological sciences 13 27649659
2014 The upstream stimulatory factor USF1 is regulated by protein kinase CK2 phosphorylation. Cellular signalling 13 25194820
2013 Molecular characterization, expression patterns, and association analysis with carcass traits of porcine USF1 gene. Applied biochemistry and biotechnology 13 23666615
2016 miR-483 is a self-regulating microRNA and can activate its own expression via USF1 in HeLa cells. The international journal of biochemistry & cell biology 12 27693430
2010 NF-Y and USF1 transcription factor binding to CCAAT-box and E-box elements activates the CP27 promoter. Gene 12 21078375
2018 Interleukin-like EMT inducer (ILEI) promotes melanoma invasiveness and is transcriptionally up-regulated by upstream stimulatory factor-1 (USF-1). The Journal of biological chemistry 11 29871931
2017 Upstream stimulating factor1 (USF1) enhances the proliferation of glioblastoma stem cells mainly by activating the transcription of mucin13 (MUC13). Die Pharmazie 11 29441861
2014 Leishmania donovani activates uncoupling protein 2 transcription to suppress mitochondrial oxidative burst through differential modulation of SREBP2, Sp1 and USF1 transcription factors. The international journal of biochemistry & cell biology 11 24417972
2008 Interaction of USF1/USF2 and alpha-Pal/Nrf1 to Fmr-1 promoter increases in mouse brain during aging. Biochemical and biophysical research communications 11 18782566
1990 A yeast homolog of the human UEF stimulates transcription from the adenovirus 2 major late promoter in yeast and in mammalian cell-free systems. Nucleic acids research 10 2204028

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