| 1988 |
OTF-1 (POU2F1) binds the TAATGARAT sequence (overlapping the octamer motif) and the herpesvirus transactivator Vmw65 (VP16) induces formation of a higher-order complex that includes OTF-1 and at least one additional cellular factor; VP16 does not bind DNA directly but interacts with OTF-1 to stimulate HSV IE gene transcription. |
Affinity purification of OTF-1/OTF-2; band-shift (EMSA) assay; complementation experiments with OTF-1-depleted nuclear extracts |
Proceedings of the National Academy of Sciences of the United States of America |
High |
2842768
|
| 1990 |
The 160-amino-acid POU domain of Oct-1 is sufficient to stimulate adenovirus DNA replication in vitro in an octamer-dependent manner; the POU-specific subdomain is required for full activity, whereas the homeodomain alone has weak DNA-binding activity and paradoxically inhibits replication; the DNA replication-stimulating domain does not coincide with the transcription activation domain, indicating distinct mechanisms. |
Vaccinia expression system overproduction of Oct-1, Oct-2, and deletion mutants; in vitro adenovirus DNA replication assay; DNA-binding assays |
The EMBO journal |
High |
2347308
|
| 1990 |
Purified OTF-1 and OTF-2 show indistinguishable DNA-binding affinities and contacts on both the H2B and immunoglobulin promoters; each can activate transcription from either promoter in OTF-depleted extracts, but full immunoglobulin gene activation requires an additional B-cell-specific component that interacts with the OTFs. |
Purification of OTF-1/OTF-2 from HeLa and B cells; high-resolution DNase I footprinting; mobility shift/competition assays; in vitro transcription reconstitution with OTF-depleted extracts |
Molecular and cellular biology |
High |
2123291
|
| 1991 |
Oct1 undergoes a complex temporal program of phosphorylation during the cell cycle; a p34cdc2-related kinase active during mitosis is responsible for at least one mitotic phosphorylation, and multiple kinases and phosphatases appear to be involved in generating distinct phosphopeptides at specific cell cycle phases. |
Cell cycle synchronization; 2D phosphopeptide mapping; kinase activity assays |
Science (New York, N.Y.) |
High |
1887216
|
| 1994 |
A flanking cis-element adjacent to the octamer core induces a conformational change in the Oct-1 POU domain–DNA complex; this conformation is required for Vmw65 (VP16) recognition. A single substitution in the flanking signal prevents VP16 interaction without affecting overall POU binding, and a homeodomain residue mutation reverts the complex to a conformation not recognized by VP16. |
Site-directed mutagenesis of flanking cis element and homeodomain residues; EMSA; VP16 complex formation assays |
Cell |
High |
8001121
|
| 1994 |
In B cells lacking Oct2, the ubiquitous Oct1 can activate octamer-containing promoters to normal levels via a novel B-cell-specific complex containing Oct1; a second B-cell activity interacts specifically with Oct2 to confer function from distal enhancer positions, demonstrating context-dependent functional selectivity. |
Reporter gene transfection in Oct2-deficient B cell lines; EMSA to detect Oct1-containing B-cell complex |
The EMBO journal |
Medium |
8157005
|
| 1996 |
Oct-1 and Oct-2 DNA-binding site specificity is regulated in vitro by protein kinase A, protein kinase C, and casein kinase 2 in a binding-site-specific manner; inhibition of cellular phosphatases also modulates binding, and the kinase effects are phosphatase-dependent, indicating that the balance of kinase/phosphatase activity controls Oct-1 DNA-binding selectivity. |
In vitro kinase treatment of nuclear extracts; EMSA with three distinct octamer/TAATGARAT motifs; phosphatase inhibitor studies |
The Biochemical journal |
Medium |
8645173
|
| 1997 |
The POU domain of either Oct-1 or Oct-2 is sufficient to activate transcription from both Ig and H2B promoters in B cells; in combination with specific distal enhancers, Oct-1 is preferentially more potent and this preference depends on a region external to the POU domain. |
Altered DNA-binding specificity mutants of Oct-1 and Oct-2; reporter gene assays in B cells with varied promoter/enhancer combinations |
The EMBO journal |
High |
9384588
|
| 1997 |
VP16 is phosphorylated by casein kinase II (CKII) at Ser375 in vitro and in nuclear extracts; Ser375 is the critical residue required for complex formation with Oct-1 and HCF, and its substitution to alanine abolishes CKII phosphorylation and virtually eliminates Oct-1/HCF complex formation and transactivation in vivo. |
In vitro CKII phosphorylation of purified wild-type and mutant VP16; complex formation assays; transactivation assays |
The EMBO journal |
High |
9171355
|
| 1998 |
OTF1 (Oct-1) can bind to its cognate site on a histone H3/H4 tetramer particle (but not on the full octamer particle) assembled on the MMTV promoter; SWI/SNF remodeling of the octamer particle generates a DNase I pattern indistinguishable from the tetramer, suggesting that SWI/SNF promotes Oct-1 access by removing H2A/H2B. |
In vitro chromatin reconstitution with recombinant histones; site-directed hydroxyl radical mapping; DNase I footprinting; transcription factor binding assays; SWI/SNF remodeling assay |
Journal of molecular biology |
High |
9614938
|
| 1999 |
Crystal structure of a ternary complex (OCA-B peptide / Oct-1 POU domain / octamer DNA) at 3.2 Å resolution reveals that OCA-B binds in the major groove near the center of the octamer, forming hydrogen bonds with the adenine at position 5 of the DNA; a short OCA-B α-helix contacts a hydrophobic pocket on the POU-specific domain, providing structural basis for cofactor selectivity in immunoglobulin transcription. |
X-ray crystallography at 3.2 Å |
Genes & development |
High |
10541551
|
| 1999 |
Oct-1 functionally interacts with retinoid X receptor (RXR) via the POU homeodomain (not POU-specific domain) and RXR's C/D domains; Oct-1 reduces TR/RXR binding to thyroid hormone response elements (TREs) and represses T3-dependent transcription by altering DNA-binding ability of TR/RXR heterodimers. |
In vitro pull-down with RXR deletion mutants; EMSA; transient transfection reporter assays in COS1 cells |
The Journal of biological chemistry |
Medium |
10383413
|
| 1999 |
Oct1 and YY1 bind to a novel negative regulatory element at positions -90 to -79 of the human IL-5 promoter; substitution mutations abolishing their binding significantly increase IL-5 promoter activity in activated T cells, establishing Oct1 as a transcriptional repressor at this locus. |
DNase I footprinting; EMSA; site-directed mutagenesis; reporter gene transfection in T cells |
The Journal of allergy and clinical immunology |
Medium |
10359895
|
| 2000 |
Isothermal titration calorimetry of Oct-1 POU domain binding to the octamer reveals a large negative heat capacity change exceeding empirical predictions from buried surface area; proteolysis studies indicate this discrepancy arises from partial folding of the POU domain upon DNA binding; six charged protein-DNA phosphate contacts are identified. |
Isothermal titration calorimetry; limited proteolysis of free vs. DNA-bound protein |
Biochemistry |
Medium |
10858307
|
| 2001 |
The Oct-1 N-terminal activation region plus POU domain (residues 1–445) is sufficient for in vitro transcription stimulation from an immunoglobulin promoter with Bob1 (OCA-B) and from the HSV ICPO promoter with VP16; the activation domains of Oct-1 and Bob1 are largely unstructured and do not physically interact, implying their synergy requires co-recruitment of common factors. |
Recombinant protein expression and purification; in vitro transcription assay; NMR/spectroscopic characterization of activation domain structure |
Biochemistry |
Medium |
11380252
|
| 2002 |
BRCA1 activates the GADD45 promoter through OCT-1 and CAAT motifs; BRCA1 physically associates with transcription factors Oct-1 and NF-YA (which bind these motifs) as shown by biotin-streptavidin pull-down and co-immunoprecipitation; immunodepletion of Oct-1 or NF-YA, or mutation of their binding sites, disrupts BRCA1 binding to the GADD45 promoter. |
Biotin-streptavidin pull-down; co-immunoprecipitation; site-directed mutagenesis; chromatin immunoprecipitation; reporter assays |
The Journal of biological chemistry |
High |
11777930
|
| 2003 |
STAT5A/B and Oct-1 form a stable complex on the cyclin D1 proximal promoter; cytokine-activated STAT5 requires an adjacent octamer element constitutively occupied by Oct-1 for stable recruitment in vitro; STAT5 interacts with Oct-1 in vivo via a carboxy-terminal STAT5 motif similar to known Oct-1 POU-interacting motifs found in OBF-1/Bob and SNAP190. |
EMSA; co-immunoprecipitation in vivo; reporter assays; mutational analysis of promoter elements |
Molecular and cellular biology |
High |
14645506
|
| 2003 |
OBF1 stabilizes Oct1 POU dimer–DNA interactions on PORE-type sequences, alleviates DNA sequence requirements for Oct1 dimerization, and overrides Oct1 interface mutations that abolish PORE-mediated dimerization; the PORE-type Oct1/Oct2 dimer (not monomer) is the primary OBF1 target. |
In vitro EMSA with purified proteins; mutagenesis of Oct1 dimer interface; reporter gene assays in B cells |
The EMBO journal |
High |
12727885
|
| 2005 |
Prolactin decreases Oct-1 binding to the proximal cyclin D1 promoter (via a region spanning -254 to -180), and this decreased binding correlates with increased PRL-responsiveness; proximal promoter activity remains Stat5-dependent, identifying an inhibitory role for Oct-1 at this locus that is relieved by cytokine signaling. |
EMSA; promoter deletion and mutational analysis; reporter assays in multiple cell lines |
Molecular and cellular endocrinology |
Medium |
15885880
|
| 2006 |
Sox2 and Oct-1 (Pou2f1) interact cooperatively on composite Sox/Oct DNA-binding sites to transactivate the Pax6 lens ectoderm enhancer; genetic combination of Sox2 and Pou2f1 mutant alleles causes failure of lens and nasal placode induction phenocopying Pax6 null embryos; the same composite binding sites are essential for Pax6 enhancer activity in vivo. |
Genetic epistasis (compound heterozygous mouse mutants); in vitro transactivation assays; transgenic mouse enhancer assays; identification of cooperative DNA-binding sites |
Developmental biology |
High |
17140559
|
| 2007 |
DNA-PK phosphorylates a cluster of 13 Ser/Thr residues within the N-terminal transcriptional regulatory domain of Oct-1 following ionizing radiation; these phosphorylations are required for Oct-1-mediated cell survival after DNA damage; Ser/Thr-to-Ala substitution eliminates IR-induced phosphorylation and prevents rescue of Oct-1−/− MEF survival. |
In vivo phosphorylation assays after IR; site-directed mutagenesis (Ser/Thr → Ala); rescue of Oct-1−/− MEFs; ChIP for RNA PolII/TBP/H4Ac at H2B promoter |
Oncogene |
High |
17213819
|
| 2007 |
Oct-1 binds the p15(INK4b) promoter in vitro and in vivo; the Oct-1 binding site functions as a silencer; SMRT and HDAC1 are present at the p15 proximal promoter; Oct-1−/− MEFs show elevated p15 protein; HDAC inhibitor activates p15 in wild-type but not Oct-1−/− MEFs, establishing HDAC-dependent transcriptional repression of p15 by Oct-1. |
EMSA; ChIP; HDAC inhibitor treatment; comparison of wild-type vs. Oct-1−/− MEFs |
FEBS letters |
High |
17316622
|
| 2009 |
Oct1 is dynamically phosphorylated in vivo following oxidative and genotoxic stress; stress regulates the DNA-sequence selectivity of both Oct1 and Oct4; mutation of conserved phosphorylation target residues in the DNA-binding domain confirms their role in regulating binding selectivity; ChIP shows stress-inducible association of Oct1 with a distinct set of in vivo targets. |
In vivo phosphorylation analysis; mutagenesis of Oct1/Oct4 POU domain residues; ChIP; Oct1 target gene screen under stress conditions |
Genes & development |
High |
19171782
|
| 2009 |
Oct-1 functions as a repressor of Cdx-2 (proglucagon gene activator) in pancreatic and intestinal endocrine cells; cAMP elevation activates EPAC, leading to enhanced Oct-1 phosphorylation and nuclear exclusion, reducing Oct-1 and co-repressor association with the Cdx-2 promoter and increasing proglucagon/proinsulin mRNA. |
ChIP; pharmacological cAMP elevation; subcellular fractionation; reporter assays |
The Journal of biological chemistry |
Medium |
19617623
|
| 2010 |
Oct1 recruits the Jmjd1a/KDM3A lysine demethylase to remove inhibitory H3K9me2 marks and block repression at Polr2a and Ahcy target loci in fibroblasts; at the Il2 locus in T cells and Cdx2 locus in colon cancer cells, Oct1 recruits the NuRD chromatin-remodeling complex to promote repression, but can switch to Jmjd1a recruitment for anti-repression — establishing Oct1 as a switchable stabilizer of repressed and inducible states. |
ChIP for histone marks and co-factors; siRNA knockdown; purified T cells and colon cancer cell lines |
The Journal of biological chemistry |
High |
21051540
|
| 2010 |
Oct1 is required for mTOR-induced G1 cell cycle arrest: Oct1−/− MEFs bypass G1 arrest induced by glucose/amino acid starvation or rapamycin; Oct1 controls transcription of CDK inhibitor p27(Kip1) downstream of mTOR, and Oct1-null cells fail to upregulate p27(Kip1) in response to mTOR inhibition. |
Oct1−/− MEFs; cell cycle analysis; rapamycin treatment; glucose/amino acid starvation; qRT-PCR and protein expression of p27(Kip1) |
Cell cycle (Georgetown, Tex.) |
High |
20935455
|
| 2011 |
Oct1 is phosphorylated at S335 by the NIMA-related kinase Nek6 during M-phase, which excludes Oct1 from mitotic chromatin and concentrates phospho-Oct1 at centrosomes, mitotic spindle poles, kinetochores, and the midbody; phospho-Oct1 is subsequently modified by non-canonical K11-linked polyubiquitin chains added by the anaphase-promoting complex (APC1 interacts with Oct1-pS335); Oct1 depletion causes spindle morphogenesis defects in Xenopus egg extracts. |
siRNA knockdown; phospho-specific antibodies; immunofluorescence; Xenopus egg extract spindle assay; co-immunoprecipitation with APC1; ubiquitin linkage-specific analysis |
PloS one |
High |
21897860
|
| 2011 |
NMR (residual dipolar coupling and paramagnetic relaxation enhancement) characterization of Oct1 DNA search reveals that the POU(HD) domain searches DNA primarily by rotation-coupled sliding (intramolecular translocation) while the POU(S) domain acts as an antenna to promote intersegment transfer via a bridged intermediate; cross-talk between POU(S) and POU(HD) ensures efficient sampling of DNA. |
Residual dipolar coupling (RDC) NMR; paramagnetic relaxation enhancement (PRE) NMR; specific and nonspecific DNA complexes |
Proceedings of the National Academy of Sciences of the United States of America |
High |
21555551
|
| 2013 |
Oct1 is modified by O-linked β-N-acetylglucosamine (O-GlcNAc) at T255 and S728; under anchorage-independent overgrowth conditions, O-GlcNAcylation correlates with increased Oct1 binding to the Gadd45a promoter and transcriptional repression; upon acute nutrient starvation, Oct1 mediates Gadd45a activation; both O-GlcNAc sites are important for both repression and activation, identifying Oct1 as a metabolic/stress signal integrator. |
O-GlcNAc site mapping; mutagenesis of O-GlcNAc sites; ChIP; reporter assays; identification of ubiquitination sites |
FASEB journal |
Medium |
23580612
|
| 2015 |
Oct1 and its cofactor OCA-B are selectively required for in vivo generation of CD4+ memory T cells and their response to antigen reencounter; mechanistically, OCA-B recruits the histone demethylase Jmjd1a to maintain poised (H3K9me2-low) states at target loci including Il2, Ifng, and Zbtb32 in resting but previously stimulated CD4+ T cells; ChIPseq identifies ~50 direct Oct1/OCA-B target genes. |
In vivo T cell memory assays (adoptive transfer); ChIPseq; ChIP-qPCR for H3K9me2; gene expression analysis; OCA-B conditional knockout |
The Journal of experimental medicine |
High |
26481684
|
| 2015 |
ACK1 phosphorylates AKT (Thr308/Ser473) to activate the AKT pathway, which upregulates POU2F1 transcription factor; POU2F1 then directly binds the promoter of ECD (ecdysoneless homologue) to drive ECD expression, thereby promoting EMT, migration, and invasion in gastric cancer cells. |
SILAC proteomics; ChIP for POU2F1 at ECD promoter; reporter assays; overexpression/knockdown; in vivo metastasis assay |
The Journal of pathology |
Medium |
25678401
|
| 2016 |
Oct1 is recruited to the FILIP1L promoter following doxorubicin treatment (TOP2 poison) and facilitates FILIP1L expression, which mediates apoptosis; FILIP1L induction is specific to TOP2-targeting drugs (not UV or TOP2 catalytic inhibitors), establishing Oct1 as a mediator of genotoxic-stress-induced pro-apoptotic transcription. |
shRNA screen; ChIP showing Oct1 relocalization to FILIP1L promoter; reporter assays; drug specificity comparisons |
PloS one |
Medium |
22900064
|
| 2016 |
Oct1 is recruited to androgen receptor (AR)-binding enhancer/promoter regions genome-wide in prostate cancer cells (ChIP-seq); Oct1 facilitates AR signaling and a major Oct1/AR co-regulated target is ACSL3; pyrrole-imidazole polyamides targeting the Oct1-binding sequence block Oct1 chromatin association, suppress ACSL3 induction, and inhibit castration-resistant tumor growth in vivo. |
ChIP-seq; ChIP-qPCR; polyamide treatment; xenograft tumor growth assays |
Oncogene |
High |
27270436
|
| 2017 |
POU2F1 directly binds the ALDOA promoter to enhance its transcriptional activity, upregulating aldolase A and thereby enhancing aerobic glycolysis and the pentose phosphate pathway in colon cancer cells; this POU2F1-ALDOA axis reduces oxidative stress, promotes proliferation, and decreases oxaliplatin sensitivity. |
ChIP for POU2F1 at ALDOA promoter; reporter assays; gain/loss of function with functional metabolic readouts |
Oncogene |
Medium |
34997215
|
| 2017 |
BRCA1 promotes Oct1 ubiquitylation and degradation via its N-terminal E3 ubiquitin ligase activity (with BARD1); BRCA1 E3 ligase mutation elevates Oct1 protein and skews cells toward glycolysis; mutation of two ubiquitylated Oct1 lysines insulates Oct1 against BRCA1-mediated destabilization; CRISPR Oct1 deletion reverts the glycolytic phenotype caused by BRCA1 E3 mutation. |
BRCA1 E3 ligase mutants; CRISPR Oct1 deletion; ubiquitylation assays; metabolic profiling; RNAseq; xenograft assays |
Molecular cancer research : MCR |
High |
29330289
|
| 2017 |
POU2F1 binds promoters of fibrosis repressors IL1R2, CD69, and TGIF2 in cardiac fibroblasts (shown by ChIP); pathological substrate stiffness upregulates POU2F1, which represses these fibrosis repressors, promoting cardiac fibroblast-to-myofibroblast differentiation; POU2F1 knockdown upregulates the repressors and attenuates differentiation. |
ChIP for POU2F1 at repressor promoters; polyacrylamide hydrogel stiffness model; gain/loss of function; mouse myocardial infarction model |
Science China. Life sciences |
Medium |
32617828
|
| 2017 |
POU2F1 directly suppresses NPR3 promoter activity by binding the -900 to -800 bp region (dual-luciferase and site-directed mutagenesis); loss of NPR3 (suppressed by POU2F1) activates the PI3K/AKT pathway to promote osteosarcoma cell proliferation. |
Dual-luciferase reporter assay; site-directed mutagenesis of POU2F1 binding site; gain/loss of function; PI3K/AKT pathway readouts |
Cellular signalling |
Medium |
34229087
|
| 2017 |
OCT1 is an AR collaborative transcription factor in CRPC cells; ChIP-seq in 22Rv1 CRPC cells reveals expanded OCT1 binding regions vs. LNCaP, with CRPC-specific target genes including ANLN (anillin); ANLN knockdown impairs cell growth and cell cycle progression, identifying it as a functional Oct1/AR co-regulated target in advanced prostate cancer. |
ChIP-seq; microarray; ChIP-qPCR; siRNA knockdown; cell cycle analysis |
Endocrinology |
Medium |
30649323
|
| 2019 |
CKIP-1 interacts with the proteasome activator REGγ and targets Oct-1 for degradation, thereby suppressing Oct-1-driven transcription of the scavenger receptor LOX-1; Ckip-1 deficiency in macrophages specifically upregulates LOX-1 (not CD36 or SR-A), increases lipoprotein uptake and foam cell formation, and accelerates atherosclerosis in mice. |
Co-immunoprecipitation of CKIP-1/REGγ/Oct-1; protein stability assays; ChIP for Oct-1 at LOX-1 promoter; Ckip-1 KO mice; bone marrow transplantation |
Nature communications |
High |
30683852
|
| 2019 |
Oct1/Pou2f1 deletion in mouse colon stem cells selectively blocks recovery from dextran sodium sulfate injury and reduces tumorigenicity in a chemical carcinogen model, while loss of one or both Oct1 alleles progressively increases tumor burden in an Apc loss-of-heterozygosity model; Oct1 ChIP-seq in HCT116 cells identifies targets associated with mitotic stability, metabolism, and stress response. |
Conditional Oct1 deletion in gut stem cells; DSS colitis model; chemical and Apc-LOH tumor models; ChIP-seq |
PLoS genetics |
High |
31059499
|
| 2021 |
The lncRNA MIR210HG interacts directly with OCT1 in the nucleus of GBM cells; this interaction promotes OCT1-mediated transcription of IGFBP2 and FGFR1, driving hypoxic GBM stemness, invasion, and temozolomide resistance. |
RNA immunoprecipitation (direct OCT1-MIR210HG interaction); nuclear fractionation; RNA-seq; gene knockdown; in vitro and in vivo growth assays |
Cancer science |
Medium |
34897892
|
| 2021 |
YES1 kinase phosphorylates OCT1 on tyrosine residues (identified by unbiased phospho-proteomics); pharmacological or genetic inhibition of YES1 reduces OCT1 transporter activity (SLC22A1) and modulates hepatic isobutyryl-L-carnitine levels in vivo, demonstrating post-translational regulation of OCT1 by tyrosine phosphorylation. |
Phospho-proteomics screen; genetic/pharmacological YES1 inhibition; targeted metabolomics for OCT1 biomarker |
Frontiers in pharmacology |
Medium |
33790797
|
| 2022 |
Exercise training activates AMPK, which downregulates C/EBPβ, the transcription factor that drives POU2F1 expression; POU2F1 overexpression nullifies exercise-training benefits on cardiac fibrosis; C/EBPβ binds and activates the POU2F1 promoter (validated by dual-luciferase reporter assay), establishing the AMPK→C/EBPβ→POU2F1 axis in cardiac fibroblasts. |
Dual-luciferase reporter assay for C/EBPβ binding to POU2F1 promoter; AAV9-mediated POU2F1 overexpression in vivo; AMPK agonist/inhibitor; RNA-seq |
Journal of sport and health science |
Medium |
36374849
|
| 2024 |
Neuronal miR-9 targets Oct-1 (and Onecut family members) to repress HSV-1 lytic gene activation and promote latency; knockdown of Oct-1 via miR-9 reduces HSV-1 replication, while overexpression of Oct-1 (or Onecutproteins) increases HSV-1 replication and reactivation; Oct-1 is thus a host co-activator of HSV transcription regulated by neuronal miR-9. |
Functional miRNA screen; luciferase-expressing HSV-1; lentiviral miR-9 expression; siRNA knockdown; overexpression in Neuro-2a, iPSC-derived neurons, and primary mouse neurons; ChIP-seq; ATAC-seq; RNA-seq |
Nature communications |
High |
38443365
|