| 1998 |
USF1 binds cooperatively with Stat1 to the GAS/E-box motif in the CIITA promoter IV; Stat1 can only bind to the GAS site in the presence of USF1 at the adjacent E-box, establishing a cooperative protein-DNA interaction required for IFNγ-induced MHC class II expression. |
EMSA (cooperative binding assays), transactivation reporter assays, in vivo footprinting |
Immunity |
High |
9491997
|
| 1997 |
USF1 physically and functionally interacts with TFII-I (a 120 kDa factor binding both Inr and E-box elements); domains of USF1 required for independent and synergistic transcriptional activation were mapped, and the two factors act synergistically to activate transcription through both Inr and E-box elements of the adenovirus major late promoter. |
cDNA cloning, ectopic expression, in vivo transcription assays, domain deletion analysis |
The EMBO journal |
High |
9384587
|
| 2001 |
USF1 is phosphorylated and activated by the stress-responsive p38 kinase following UV irradiation, and is required for UV-induced activation of the Tyrosinase promoter in melanocytes; Usf1 knockout melanocytes fail to activate Tyrosinase expression in response to UV. |
In vitro kinase assay (p38 phosphorylation of USF1), USF1 knockout mouse melanocytes, reporter gene assays, functional UV response assays |
The EMBO journal |
High |
11532965
|
| 1998 |
USF1 directly interacts with Ets-1 through their DNA-binding domains; the USF1–Ets1 complex binds adjacent E-box and Ets sites in the HIV-1 LTR distal enhancer and synergizes for DNA binding and transactivation in T cells. A dominant-negative Ets-1 mutant inhibits USF1-mediated transactivation in an Ets-site-independent but USF1-binding-surface-dependent manner. |
Yeast one-hybrid screen, co-IP/pulldown (binding surface mapping), reporter assays with site-directed mutations, dominant-negative constructs |
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; USF1 protein level is dramatically increased in liver of refed rats (regulated by nutritional state), while a 17-kDa USF1-related protein is inversely regulated, suggesting USF1 mediates insulin/nutritional regulation of FAS transcription. |
Gel shift competition assay, USF antibody supershift, UV cross-linking, western blotting (nutritional regulation) |
The Journal of biological chemistry |
High |
7499393
|
| 2007 |
USF1 directly interacts with the histone H4R3-specific methyltransferase PRMT1, and forms a complex with PRMT1, PCAF, and SRC-1 having both H4R3 methyltransferase and HAT activities. USF1 siRNA knockdown causes localized loss of H4R3 methylation and euchromatin-associated histone modifications at the chicken beta-globin insulator, and a dominant-negative USF1 peptide abolishes insulator barrier function. |
Co-immunoprecipitation, histone methyltransferase assay, HAT assay, siRNA knockdown with ChIP, dominant-negative peptide functional assay |
Molecular and cellular biology |
High |
17846119
|
| 2004 |
UV-induced activation of POMC and MC1R promoters is mediated by USF1 through p38 stress-activated kinase signaling; melanocytes from Usf1−/− mice exhibit a defective UV response and fail to activate POMC and MC1R expression after UV irradiation. |
Knockout mouse melanocytes (USF1−/−), reporter assays, RT-PCR for gene expression |
The Journal of biological chemistry |
High |
15358786
|
| 2009 |
In response to DNA damage, oxidative stress, and cellular infection, USF1 is acetylated in a phospho-Thr-153-dependent fashion (p38-mediated phosphorylation on Thr-153 is a prerequisite for acetylation). Phospho-acetylated USF1 is nuclear, binds DNA, but displays altered (reduced) transcriptional activation properties toward pigmentation and cell cycle genes. |
In vitro kinase assay (p38 on USF1 Thr-153), acetylation assays, site-directed mutagenesis, nuclear fractionation, reporter assays |
The Journal of biological chemistry |
High |
19389701
|
| 1999 |
DNA-binding activity of USF1 is greatly increased by phosphorylation by cyclin A2-p34(cdc2) or cyclin B1-p34(cdc2) complexes in vitro; the phosphorylation site was localized to residues 143–197, a region outside the minimal DNA-binding domain but overlapping the USF-specific region. |
In vitro kinase assay (cyclinA2/B1-cdc2 with recombinant USF1), EMSA (DNA binding), deletion/phosphorylation mapping |
The Biochemical journal |
High |
10548544
|
| 2013 |
USF1 competes with the CLOCK:BMAL1 complex for binding to E-box sites in circadian target genes. A SNP in the Usf1 promoter elevates USF1 transcript and protein, which suppresses the ClockΔ19 mutant behavioral phenotype. Saturation binding experiments show reduced affinity of the CLOCKΔ19:BMAL1 complex for E-box sites, permitting increased USF1 genome-wide occupancy. |
Genetic suppressor mapping, SNP identification, quantitative ChIP (genome-wide USF1 occupancy), saturation binding experiments, behavioral circadian phenotyping |
eLife |
High |
23580255
|
| 2014 |
USF1 stabilizes p53 protein by preventing MDM2-mediated p53 degradation; loss of USF1 enhances p53–MDM2 complex formation, leading to proteasomal degradation of p53. A USF1 truncated protein lacking its DNA-binding and transactivation domains is sufficient to restore p53 stability, indicating a non-transcriptional mechanism. |
Co-immunoprecipitation (USF1/p53/MDM2), Usf1 KO mouse cells, siRNA knockdown, re-expression of truncated USF1, Nutlin-3 comparison, western blotting |
PLoS genetics |
High |
24831529
|
| 2019 |
H. pylori delocalizes USF1 into cytoplasmic foci near cell membranes, prevents nuclear USF1/p53 complex formation, and promotes MDM2-mediated degradation of p53. USF1 physically interacts with p53 in the nucleus; this complex is disrupted by H. pylori infection, impairing p53 transcriptional function and promoting genetic instability. |
Immunofluorescence (subcellular localization), Co-IP (USF1/p53), Usf1−/− mouse in vivo carcinogenesis model, genotoxin (camptothecin) challenge |
Gut |
High |
31822580
|
| 2013 |
USF1 recruits the hSET1A histone H3K4 methyltransferase complex to the HoxB4 promoter, governing H3K4me3 modifications and transcription preinitiation complex assembly. Disruption of USF1 by dominant-negative AUSF1 or siRNA against hSET1A reduces mesoderm marker expression and inhibits lineage differentiation; ectopic USF1 in ESCs promotes mesoderm/hematopoietic differentiation. |
ChIP (H3K4me3, USF1, hSET1A at HoxB4 promoter), dominant-negative overexpression, RNAi knockdown, ESC differentiation assays |
PLoS genetics |
High |
23754954
|
| 2002 |
USF1 binds to the E-box motif at −160 to −165 in the PAI-1 proximal promoter in wound-activated keratinocytes; E-box binding activity increases within 2 hours of monolayer scrape injury; USF1 isolated by PAI-1 promoter-DNA affinity chromatography is almost exclusively phosphorylated. Antisense PAI-1 knockdown significantly impairs keratinocyte migration. |
EMSA, UV crosslinking, DNA affinity chromatography, immunocytochemistry (USF1 localization), antisense knockdown (migration assay) |
Journal of cell science |
Medium |
12235287
|
| 2002 |
USF1 (and USF2) bind to an E-box at −893/−888 of the murine iNOS promoter and trans-repress basal and IL-1β-induced iNOS transcription in mesangial cells; mutation of the E-box augments iNOS response to IL-1β, and cotransfection of dominant-negative USF-2 or E-box decoys augments IL-1β stimulation of iNOS promoter activity. |
Site-directed mutagenesis, EMSA (supershift), cotransfection of USF expression vectors and dominant-negative mutants, luciferase reporter assay |
American journal of physiology. Cell physiology |
High |
12225970
|
| 1997 |
USF1 competitively binds to the xenobiotic response element (XRE) of the rabbit CYP1A1 gene, overlapping the AhR·Arnt binding site, and antagonizes AhR·Arnt-mediated CYP1A1 induction; transfection of USF1 expression vector blocks AhR/Arnt interaction with XRE and suppresses CYP1A1 mRNA induction. |
Supershift EMSA, competition gel shift, transfection with USF1 expression vector, S1 nuclease protection assay |
The Journal of biological chemistry |
High |
9374477
|
| 2001 |
USF1 interacts with the MTF-1 metalloregulatory factor to cooperatively regulate MT-I gene expression in response to zinc in visceral endoderm cells; USF1 binds an E-box1 sequence at −223 bp in the MT-I promoter, and MTF-1 is absolutely essential while USF1 is required for optimal expression. |
USF1 and MTF1 knockout mouse embryos (genetic epistasis), promoter reporter assays, zinc deprivation/repletion |
The EMBO journal |
High |
11230134
|
| 2012 |
USF1 is required for UV-induced upregulation of DNA repair genes CSA and HR23A (TCR and GGR NER components) through a p53-independent mechanism; Usf1 knockout mice display compromised DNA repair after UV irradiation. |
In vitro and in vivo UV irradiation assays, Usf1 KO mouse model, gene expression analysis, ChIP |
PLoS genetics |
High |
22291606
|
| 2002 |
USF1 binds to the E-box at −47 in the cardiac α-MHC promoter (hemodynamic response element); phosphorylation of USF1 by PKC or PKA in vitro increases its DNA-binding activity to the HME. PKC-mediated phosphorylation also causes USF1 multimerization. In vivo, USF1 is phosphorylated in spontaneously contracting cardiomyocytes, correlating with enhanced HME binding and α-MHC promoter activity. |
In vitro kinase assay (PKC, PKA, CK2 with purified rat USF1), gel shift assay, 2D gel electrophoresis of in vivo phosphorylated USF1, luciferase reporter assay |
American journal of physiology. Heart and circulatory physiology |
High |
12063293
|
| 2014 |
Protein kinase CK2 phosphorylates USF1 at threonine 100 (identified by deletion and point mutants); inhibition of CK2 kinase activity enhances USF1–USF2 heterodimerization and stimulates transcription from glucokinase and fatty acid synthase promoters but not the heme oxygenase-1 promoter. |
In vitro CK2 kinase assay, deletion and point mutant mapping (Thr100), USF1-USF2 binding assay, transactivation reporter assay |
Cellular signalling |
High |
25194820
|
| 2017 |
CK2 phosphorylation of USF1 modulates USF1–PDX-1 interaction and represses PDX-1 promoter transcription; inhibition of CK2 abrogates USF1 binding to the PDX-1 promoter and relieves USF1-mediated transrepression, enhancing insulin expression and secretion from primary islets. |
Transactivation assay, promoter binding assay with phosphomutant USF1, CK2 inhibitors, Co-IP (USF1–PDX1 interaction), primary islet insulin secretion assay |
Scientific reports |
Medium |
29180680
|
| 2016 |
USF1 deficiency in mice activates brown adipose tissue (BAT) and enhances adrenergic thermogenesis; USF1 silencing in brown adipocytes amplifies the adrenergic response. Usf1 inactivation directs triglycerides from circulation to BAT via a lipoprotein lipase-dependent mechanism, increasing energy expenditure and improving cardiometabolic health. |
Usf1 knockout mice (diet-induced dyslipidemia model), USF1 siRNA in brown adipocytes (adrenergic response), lipoprotein lipase activity assays, metabolic phenotyping, mitochondrial complex quantification |
Science translational medicine |
High |
26819196
|
| 2003 |
USF1 and USF2 bind to an E-box (CAGCTG) in the first intron of the FcεRI alpha chain gene; this complex activates FcεRI alpha chain expression. Overexpression of USF2 antisense repressed FcεRI alpha chain promoter activity and decreased alpha chain mRNA levels in mast cell lines. |
EMSA with antibody supershift and in vitro translated USF1/USF2, reporter assay (orientation/position dependence), USF2 antisense overexpression |
European journal of immunology |
Medium |
11180124
|
| 2011 |
USF1 is activated by GSK3 phosphorylation (at Thr-153 and Ser-186); upon PI3K inhibition, Max/Mnt complexes dissociate from target gene promoters and USF1 (and MITF) bind E-boxes to induce proapoptotic and cell cycle arrest genes. siRNA against USF1 reduces transcriptional induction of these genes and protects cells from apoptosis. |
ChIP (Max, Mnt, USF1, MITF binding), RNAi (USF1, MITF, FoxO3a), in vitro GSK3 phosphorylation (Thr153/Ser186 identified), PI3K inhibitor treatment |
The Journal of biological chemistry |
High |
21873430
|
| 2008 |
Retinoic acid triggers a feed-forward transcriptional loop in which CREB directly mediates early-phase MKP1 induction, and CREB indirectly induces USF1, which then mediates the later phase of MKP1 stimulation; both CREB and USF1 bind the MKP1 promoter (confirmed by ChIP and gel shift). Silencing USF1 with siRNA blocks the late-phase biological effects of retinoic acid on HIV-infected podocytes. |
Gel shift assay, ChIP (USF1 binding to MKP1 promoter), luciferase reporter with CRE/Ebox mutations, siRNA knockdown (USF1, CREB, MKP1) |
Molecular and cellular biology |
High |
18625721
|
| 2007 |
v-Src recruits HDAC1 into a USF1–Sp1–Sp3 complex at the SSeCKS alpha promoter to repress its transcription; v-Src does not alter USF1 binding at the E-box but increases Sp1/Sp3 binding at the GC-box. HDAC inhibitor treatment restores SSeCKS transcript levels; knockdown of HDAC1 is necessary and sufficient for repression of alpha promoter activity. |
Promoter deletion analysis, ChIP (HDAC1, USF1, Sp1/Sp3 recruitment), HDAC inhibitor (TSA) rescue, Co-IP, siRNA knockdown of HDAC1 |
The Journal of biological chemistry |
High |
17626016
|
| 2016 |
USF1 acetylation (induced by HDAC2/3 inhibitor apicidin) increases USF1 association with HDAC2/3 and with the ADAM10 promoter, thereby increasing ADAM10 transcription; USF1 knockdown prevents apicidin-mediated ADAM10 upregulation. ERK signaling is required for apicidin's effect on ADAM10 but does not affect USF1 phosphorylation. |
Luciferase reporter assay, siRNA knockdown (USF1, HDAC2/3), Co-IP (USF1–HDAC2/3 interaction), ChIP (USF1 binding to ADAM10 promoter), ERK inhibitor experiments |
FASEB journal |
Medium |
28003340
|
| 2023 |
PTP4A1 dephosphorylates USF1 at S309, which increases USF1 transcriptional activity and induces A20 (TNFAIP3) expression, thereby inhibiting NF-κB-mediated vascular inflammation. Loss of PTP4A1 reduces USF1 activity and exacerbates atherogenesis in ApoE−/− mice. |
shRNA knockdown, overexpression, luciferase reporter assay, ChIP (USF1 binding to A20 promoter), Co-IP, Ptp4a1 KO and transgenic mice, in vivo atherosclerosis model |
Cardiovascular research |
High |
36534975
|
| 2003 |
USF1 and USF2 bind to the E-box (CACGTG) in the FAS promoter insulin response sequence; USF binding sites are required for thymidylate synthase (TS) transcriptional regulation; a SNP in the second repeat of the 3R allele abolishes USF binding and reduces TS transcriptional activation. |
EMSA, chromatin immunoprecipitation (in vivo USF binding to TS tandem repeats), mutagenesis of USF sites, reporter assays |
Cancer research |
High |
12782596
|
| 2003 |
USF1 activates the COX-2 gene promoter through a proximal CRE/E-box element at −56 to −48; MEK/ERK1/2 signaling (activated by H. pylori virulence factors outside the cagPAI) mediates H. pylori-dependent USF1/-2 activation of the COX-2 promoter. |
Promoter deletion and functional reporter assay, EMSA (USF1/2 binding identification), MEK/ERK inhibitor studies |
Cellular microbiology |
Medium |
14531897
|
| 2000 |
USF1 and USF2 are major transcription factors binding the FMR1 promoter in brain and testis extracts; methylation of the FMR1 promoter affects binding of USF1 and USF2 (and abolishes alpha-Pal/Nrf-1 binding), providing a mechanism by which methylation silences FMR1 transcription beyond histone deacetylation. |
EMSA with brain and testis nuclear extracts, antibody supershift, promoter methylation and binding assays, reporter gene assays |
The Journal of biological chemistry |
Medium |
11058604
|
| 2003 |
NF-Y interacts biochemically with USF1/USF2 on the HOXB4 promoter; formation of the NF-Y/USF1/USF2 complex is required for full HOXB4 promoter activity in hematopoietic cells. NF-Y occupancy decreases with granulocytic differentiation as shown by ChIP. |
Co-immunoprecipitation (NF-Y/USF1/2 interaction), ChIP (NF-Y occupancy at HOXB4 promoter), reporter assays with binding site mutations |
Blood |
High |
12791656
|
| 2000 |
USF1 and USF2 bind to the HOXB4 promoter E-box (HXRE-2) and activate HOXB4 transcription through the MAP kinase pathway; USF1 and USF2 (but not MITF) induce the HOXB4 promoter in response to cytokines promoting stem cell self-renewal in both K562 and CD34+ hematopoietic cells. |
Yeast one-hybrid screen, EMSA, cotransfection reporter assays in K562 and primary CD34+ cells, E-box mutation analysis |
The Journal of experimental medicine |
Medium |
11085749
|
| 2004 |
USF1 (and ERα) are components of a multi-protein complex at the ERα minimal promoter; USF1 directly binds the imperfect E-box in the ERα minimal promoter (by EMSA), and ERα interacts with USF1 in vitro (GST pulldown); combined expression of Sp1, USF1, and ERα synergistically transactivates the ERα minimal promoter in MCF-7 cells. |
EMSA, GST pulldown (ERα–USF1 interaction), cotransfection reporter assay |
Breast cancer research and treatment |
Medium |
15111769
|
| 2011 |
USF1 plays a critical role in diabetic kidney disease; high glucose inhibits AMPK activity and increases USF1 nuclear translocation; USF1 knockout diabetic mice display significantly less albuminuria and mesangial matrix expansion, and reduced TGF-β1 and renin expression. AMPK activation with AICAR reduces nuclear USF1 accumulation. |
USF1 KO mouse × Akita diabetic mouse (loss-of-function + disease model), AMPK activation/inhibition in mesangial cells, nuclear fractionation (USF1 localization) |
American journal of physiology. Renal physiology |
High |
21543418
|
| 2024 |
USF1 knockdown in human macrophages decreases phagocytosis, chemotaxis, and actin content, and alters expression of adhesion and extracellular matrix remodeling genes; loss of USF1 increases macrophage cell size and alters morphology, phenocopying aging-related macrophage functional decline. |
siRNA knockdown of USF1 in human monocyte-derived macrophages, phagocytosis assay, chemotaxis assay, actin content measurement, transcriptomics |
Cell reports |
Medium |
38578825
|
| 2024 |
USF1 transcriptionally activates USP14, which promotes deubiquitination and stabilization of NLRC5, leading to Smad2/3 pathway activation and endothelial-to-mesenchymal transition (EndMT) in atherosclerosis. USF1 knockdown inhibits EndMT and delays atherosclerosis progression in ApoE−/− mice. |
Dual-luciferase reporter assay (USF1→USP14 promoter), ChIP (USF1 binding to USP14 promoter), Co-IP (USP14–NLRC5 interaction), shRNA knockdown rescue experiments, in vivo ApoE−/− mouse atherosclerosis model |
Molecular medicine (Cambridge, Mass.) |
High |
38424494
|
| 2003 |
A novel alternatively spliced isoform of human USF1 (USF1/BD), lacking the N-terminal transactivation domain, localizes to the nucleus and represses the angiotensinogen gene promoter; USF1/BD can form homodimers and heterodimers with USF1(wt) and bind E-box DNA in vitro. |
cDNA cloning, nuclear localization (ectopic expression), in vitro translation/dimerization assay, EMSA, reporter assay |
International journal of molecular medicine |
Medium |
12851711
|
| 2018 |
AKT-mediated phosphorylation of USF1 (induced by insulin via PI3K/AKT) enhances USF1 binding to the WBP2 promoter E-box and increases WBP2 transcription; USF1 is overexpressed in breast cancer cell lines and tissues and promotes cancer cell proliferation. |
Yeast one-hybrid (USF1 as E-box binder of WBP2 promoter), ChIP (USF1 binding to WBP2 promoter), tandem mass spectrometry (USF1 phosphorylation), reporter assay, insulin stimulation with AKT inhibitor |
FASEB journal |
Medium |
30183375
|
| 2022 |
USF1 drives transcription of the lncRNA FASRL through a superenhancer; FASRL in turn binds to and increases activity of ACACA (acetyl-CoA carboxylase 1), the fatty acid synthesis rate-limiting enzyme, promoting lipid accumulation in hepatocellular carcinoma. |
ChIP (USF1 binding to FASRL superenhancer), reporter assay, RNA pulldown (FASRL–ACACA interaction), in vitro and in vivo proliferation assays |
Advanced science |
Medium |
36307901
|