Affinage

ISYNA1

Inositol-3-phosphate synthase 1 · UniProt Q9NPH2

Length
558 aa
Mass
61.1 kDa
Annotated
2026-06-10
100 papers in source corpus 28 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ISYNA1 (and its yeast ortholog INO1) encodes myo-inositol-3-phosphate synthase, the enzyme catalyzing the first committed, rate-limiting step of myo-inositol biosynthesis (PMID:6374665). Active-site mutagenesis of the homologous enzyme establishes that catalysis depends on a defined set of active-site residues, a bound Zn²⁺ ion, and an NAD⁺ cofactor (PMID:14763976). In yeast, INO1 has served as a paradigm for transcriptional control coupled to lipid metabolism: its expression is repressed by inositol and choline and depends on the positive regulators Ino2p and Ino4p, two bHLH proteins that heterodimerize and bind the UAS(INO) promoter element, while neither binds DNA alone (PMID:3025587, PMID:8195172, PMID:2027776). Full derepression additionally requires cooperative Cbf1p binding at distal sites and recruitment of the Isw2p-Itc1p chromatin-remodeling complex (PMID:20935143, PMID:11489850). The repressing signal is the rate of phosphatidylcholine biosynthesis rather than any specific pathway intermediate, linking INO1 output to membrane phospholipid flux (PMID:8810347, PMID:9252414). INO1 transcription is further tuned by opposing Snf1 kinase and Sit4/Glc7 phosphatase activities that control TBP recruitment to the promoter, with Snf1 acting in part through phosphoinactivation of Acc1p (PMID:15716495, PMID:11486011, PMID:10224244). The locus is a model for nuclear-position-dependent gene regulation: activation recruits INO1 to the nuclear periphery via Scs2p and the activator Hac1p (PMID:15455074), and a promoter DNA 'zip code' interacting with the nucleoporin Nup100 confers mitotically heritable transcriptional memory through interchromosomal clustering, H2A.Z incorporation, and RNAPII-independent H3K4me2 deposited via SET3C, Leo1/Paf1, and COMPASS (PMID:20932479, PMID:26688804, PMID:35579426). In mammalian cells, human ISYNA1 is a direct p53 transcriptional target whose induction raises intracellular myo-inositol and suppresses tumor cell growth (PMID:27035231), and it acts as a tumor suppressor downstream of MSI2 through an ISYNA1→p21/ZEB-1 axis, with its expression also controlled by tissue-specific DNA methylation (PMID:32779876, PMID:21841945).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1984 High

    Established the molecular identity of the gene by showing it is the structural gene for the inositol biosynthetic enzyme, anchoring all downstream mechanistic work.

    Evidence Genetic complementation of ino1 auxotrophs with cloned DNA plus immunological detection of enzyme protein in yeast

    PMID:6374665

    Open questions at the time
    • Did not resolve enzyme catalytic mechanism or cofactor requirements
    • Mammalian ortholog function not addressed
  2. 1986 High

    Defined the gene as inositol/choline-repressible and identified the trans-acting regulators (INO2, INO4 positive; OPI1 negative) that control its expression.

    Evidence RNA blot, enzyme activity assays, and genetic analysis of ino2/ino4/opi1 mutants in yeast

    PMID:3025587

    Open questions at the time
    • Did not identify the cis-element bound by regulators
    • Molecular nature of the repressing signal unknown
  3. 1991 High

    Mapped regulation to a discrete promoter element, showing a single UAS(INO) repeat is necessary and sufficient for inositol/choline-responsive control.

    Evidence Promoter-lacZ deletion/insertion reporter dissection in yeast

    PMID:2027776

    Open questions at the time
    • Did not identify the protein binding the element
    • Differential activity among individual elements not yet resolved
  4. 1994 High

    Demonstrated the mechanistic basis of positive regulation: Ino2p and Ino4p heterodimerize and only the complex binds UAS(INO).

    Evidence In vitro translation, EMSA, and co-immunoprecipitation of Ino2p-Ino4p in yeast

    PMID:8195172

    Open questions at the time
    • Did not address how the repressor counteracts this complex
    • Chromatin context of binding not examined
  5. 1996 Medium

    Resolved the nature of the repressing signal, showing repression tracks the rate of phosphatidylcholine biosynthesis rather than any specific pathway or intermediate.

    Evidence Reporter assays across PC biosynthesis mutants with phospholipid measurements in yeast

    PMID:8810039 PMID:8810347

    Open questions at the time
    • Did not identify the molecular sensor transducing PC flux to the promoter
    • Did not connect signal to OPI1 mechanism
  6. 2001 High

    Identified opposing kinase/phosphatase and metabolic inputs (Snf1, Acc1, Reg1/Glc7) that set the activation threshold, integrating energy and fatty-acid metabolism with inositol gene control.

    Evidence Genetic suppressor screens, in vitro Acc1 enzyme assays, chemical inhibition, and reporters in yeast

    PMID:10224244 PMID:10747047 PMID:11486011

    Open questions at the time
    • Did not show direct promoter-level mechanism of Snf1/Sit4 action
    • Mammalian relevance untested
  7. 2005 High

    Showed how kinase/phosphatase balance acts mechanistically at the promoter by controlling TBP recruitment, linking TOR signaling to inositol gene transcription.

    Evidence ChIP for TBP, genetic epistasis, and rapamycin treatment in yeast

    PMID:15716495

    Open questions at the time
    • Did not define the chromatin steps downstream of TBP recruitment
  8. 2010 High

    Defined cooperative activation requiring both the Ino2p-Ino4p heterodimer and Cbf1p, with Cbf1p directing ISW2 chromatin remodeler recruitment.

    Evidence ChIP for multiple factors with genetic epistasis and reporter assays in yeast

    PMID:11489850 PMID:20935143

    Open questions at the time
    • Order of remodeling and transcription factor loading not fully resolved
  9. 2010 High

    Established the gene as a model for spatial and epigenetic transcriptional memory, linking promoter zip codes and the nuclear pore to histone variant deposition and faster reactivation.

    Evidence Locus imaging, H2A.Z ChIP, promoter MRS deletion, and nup100Δ analysis in yeast

    PMID:15455074 PMID:20932479 PMID:26688804

    Open questions at the time
    • Mechanism connecting NPC contact to histone variant incorporation incomplete
    • Conservation of positioning memory in mammals untested
  10. 2016 High

    Connected the gene to mammalian tumor suppression by establishing human ISYNA1 as a direct p53 target whose myo-inositol output restrains cell growth.

    Evidence p53 ChIP at a response element, myo-inositol measurement, and knockdown/overexpression with drug response in human cells

    PMID:27035231

    Open questions at the time
    • Mechanism by which elevated myo-inositol suppresses growth not defined
    • Did not address upstream regulators of ISYNA1 in cancer
  11. 2020 Medium

    Placed ISYNA1 in an oncogenic regulatory circuit as a p53-dependent target repressed by MSI2, acting through p21 and ZEB-1 to control proliferation and invasion.

    Evidence Knockdown/overexpression of ISYNA1 and MSI2, phenotypic assays, and rescue experiments in pancreatic cancer cells

    PMID:32779876

    Open questions at the time
    • Direct biochemical link between ISYNA1 enzymatic output and p21/ZEB-1 regulation unresolved
    • Single-lab cellular study without in vivo validation
  12. 2022 High

    Refined the chromatin basis of transcriptional memory by showing RNAPII-independent, mitotically heritable H3K4me2 deposited via SET3C, Leo1/Paf1, and COMPASS.

    Evidence ChIP after RNAPII depletion, genetic epistasis, cell-cycle inheritance tracking, and COMPASS-SET3C co-IP in yeast

    PMID:35579426

    Open questions at the time
    • Reader-to-methyltransferase spreading mechanism inferred, not directly reconstituted
    • Relevance to mammalian ISYNA1 unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the enzymatic product myo-inositol mechanistically drives mammalian growth suppression, and whether the yeast nuclear-memory paradigm operates at human ISYNA1, remain unresolved.
  • No mechanistic link established between intracellular myo-inositol levels and p21/ZEB-1 or growth control
  • No structural model of the mammalian enzyme in the corpus
  • Nuclear positioning/memory not tested for human ISYNA1

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016853 isomerase activity 2 GO:0016740 transferase activity 1
Localization
GO:0005634 nucleus 2 GO:0005635 nuclear envelope 1
Pathway
R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1430728 Metabolism 2 R-HSA-1643685 Disease 2 R-HSA-4839726 Chromatin organization 2
Partners
CBF1INO2INO4MSI2P53

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1984 The yeast INO1 gene (ortholog of ISYNA1) encodes myo-inositol-1-phosphate synthase, the enzyme catalyzing the first committed step in inositol biosynthesis; the cloned gene complemented ino1 loss-of-function mutants and restored cross-reactive enzyme protein, confirming its identity as the structural gene for inositol-1-phosphate synthase. Genetic complementation of ino1 auxotrophs with cloned DNA; antibody cross-reactivity assay for enzyme protein; Southern blot confirming unique genomic locus Proceedings of the National Academy of Sciences of the United States of America High 6374665
1986 INO1 (ISYNA1 ortholog) expression and inositol-1-phosphate synthase activity are transcriptionally repressed 12-fold by exogenous inositol and 33-fold by inositol plus choline combined; repression requires regulatory genes INO2 and INO4 (loss-of-function causes auxotrophy), and constitutive overexpression occurs in opi1 mutants. RNA blot hybridization under defined growth conditions; enzyme activity assays; genetic analysis of ino2, ino4, opi1 mutants Molecular and cellular biology High 3025587
1981 The INO1 locus (structural gene for inositol-1-phosphate synthase) was mapped to chromosome X of S. cerevisiae between ura2 and cdc6; ~70% of inositol auxotrophs carry ino1 alleles, and INO1 null mutations are not suppressible by known nonsense suppressors, suggesting premature termination is lethal. Trisomic analysis, genetic complementation, chromosomal mapping Genetics Medium 17249096
1991 A 9-bp repeated element (consensus 5'-CATGTGAAAT-3'), termed UAS(INO), in the INO1 promoter is necessary and sufficient for inositol/choline-responsive transcriptional regulation; the smallest active fragment was 40 bp containing one copy of this element. INO1 promoter-lacZ fusions with systematic deletions and oligonucleotide insertions; beta-galactosidase reporter assays Nucleic acids research High 2027776
1994 The positive regulators Ino2p and Ino4p (both bHLH proteins) form a heterodimeric complex that binds to the INO1 promoter UAS(INO) element; neither protein alone binds DNA, and the complex is identical in mobility to that formed with whole-cell extracts. In vitro translation of Ino2p and Ino4p; electrophoretic mobility shift assay (EMSA); immunoprecipitation confirming Ino2p–Ino4p protein–protein interaction in absence of DNA; competition with bHLH consensus oligonucleotide The Journal of biological chemistry High 8195172
1992 A dominant CSE1 mutation causes choline-dependent repression of INO1 (ISYNA1 ortholog) and inositol-1-phosphate synthase; choline-dependent repression requires metabolism of choline via the CDP-choline pathway, as blocking this pathway abolishes choline-induced INO1 repression. INO1-lacZ promoter fusions; Northern blot; enzyme activity assay; genetic epistasis with CDP-choline pathway mutations Journal of biochemistry Medium 1587797
1995 The SCS2 gene (encoding an integral membrane protein, VAP homolog) is a multicopy suppressor of ire15 and CSE1 mutations affecting INO1 expression; SCS2 and INO2/SCS1 (a positive regulator) both suppress these regulatory mutations, placing Scs2p in the INO1 regulatory pathway. Multicopy suppressor screen; genetic complementation; sequence analysis Journal of biochemistry Medium 8537323
1996 Repression of INO1 transcription in response to inositol requires ongoing phosphatidylcholine (PC) biosynthesis but is independent of the specific pathway (methylation vs. CDP-choline) used for PC synthesis; intermediates in these pathways are not the regulatory signal, and repression correlates with the rate of PC synthesis sustaining growth rather than absolute PC proportion. INO1-lacZ reporter assays; genetic analysis of PC biosynthesis mutants (cho2, opi3, cki1, pct1); growth and phospholipid measurements The Journal of biological chemistry Medium 8810347
1996 Individual UAS(INO) elements in the INO1 promoter differ in functionality; most native INO1 promoter elements are inactive individually, whereas all CHO2 promoter elements are active, explaining differential regulation between co-regulated genes; elements with C or A at the 5' position of the consensus are functional. Systematic placement of individual promoter fragments upstream of CYC1-lacZ reporter; beta-galactosidase assay; oligonucleotide mutagenesis of consensus first position Yeast (Chichester, England) Medium 8810039
1997 Inactivation of Sec14p (phosphatidylinositol/phosphatidylcholine transfer protein) in a cki1 background leads to increased phosphatidylcholine turnover via a phospholipase D-like mechanism, which derepresses INO1 (ISYNA1 ortholog) transcription, establishing a regulatory link between PC turnover and INO1 expression. Genetic epistasis (sec14ts cki1 double mutants); choline excretion assay; INO1-lacZ reporter; enzyme assays The Journal of biological chemistry Medium 9252414
1999 The REG1-encoded regulatory subunit of the Glc7 phosphatase is required for repression of INO1; reg1 loss-of-function suppresses inositol auxotrophy of ino4 and ino2 missense mutants and causes constitutive INO1 expression, placing Reg1p/Glc7 phosphatase activity as a positive component of INO1 repression. Separately, Snf4/Snf1 kinase activity promotes INO1 activation, as dominant SNF4 mutations suppress INO1 derepression defects. Genetic suppressor screen; INO1-lacZ reporter assays; two-hybrid interaction assay for Snf4-Snf1 interaction Genetics Medium 10224244
1999 REG1 (Glc7 phosphatase regulatory subunit) loss-of-function causes constitutive INO1 expression independently of OPI1; REG1 suppresses ino4 missense alleles but not ino2/ino4 null mutations; OPI1 protein does not bind UAS(INO) or interact with Ino2p or Ino4p directly. INO1-lacZ reporter assays in multiple mutant backgrounds; two-hybrid assays testing Opi1p-UAS(INO), Opi1p-Ino2p, Opi1p-Ino4p interactions (all negative) Genetics Medium 10747047
2001 Both lithium and valproate decrease intracellular myo-inositol levels and increase expression of INO1 (ISYNA1 ortholog) and INO2; valproate may inhibit Ino1p-catalyzed synthesis of inositol-1-phosphate directly, as valproate treatment decreases inositol monophosphate synthesis; the opi1 mutant is more resistant to lithium (but not valproate) growth inhibition, indicating different mechanisms for the two drugs. Northern blot for INO1/INO2 mRNA; inositol mass measurement; inositol monophosphate synthesis assay; growth assays in opi1 mutant The Journal of biological chemistry Medium 11278273
2001 The Snf1 kinase is required for INO1 activation; mutations in ACC1 (acetyl-CoA carboxylase) and FAS1 (fatty acid synthase beta subunit) suppress the inositol auxotrophy of snf1Δ strains by reducing Acc1 activity, which is elevated in snf1Δ cells because Snf1 normally phosphorylates and inactivates Acc1p; reduced fatty acid synthesis rate restores INO1 expression. Genetic suppressor screen; in vitro Acc1 enzyme activity assay; soraphen A (Acc1 inhibitor) growth sensitivity; INO1-lacZ reporter; conditional ACC1 expression Molecular and cellular biology High 11486011
2001 The Isw2p-Itc1p chromatin-remodeling complex represses INO1 expression; deletion of either ISW2 or ITC1 in a hac1Δ background derepresses INO1 even under inositol-repressing conditions; a truncated dominant-negative form of Itc1p suppresses the hac1Δ inositol auxotrophy by impairing Isw2p-Itc1p repressor function. Multicopy suppressor screen; INO1-lacZ reporter; genetic epistasis (isw2Δ itc1Δ hac1Δ); dominant-negative truncation analysis Journal of bacteriology Medium 11489850
2002 The unfolded protein response (UPR) pathway (Ire1p/Hac1p) is required for sustained high-level INO1 expression under inositol starvation but not for transient derepression; inactivation of Sec14p activates the UPR; the UPR is not required for INO1 regulation in the sec14ts cki1Δ background. Genetic epistasis (ire1Δ, hac1Δ combined with sec14ts cki1Δ); INO1-lacZ reporter; UPR reporter assays Genetics Medium 12242221
2003 Scs2p (yeast VAP homolog) regulates INO1 expression by controlling phosphatidylcholine synthesis through the CDP-choline pathway; scs2Δ cells have reduced INO1 mRNA but normal INO1 promoter-driven reporter activity, suggesting Scs2p acts post-transcriptionally or on mRNA stability; disruption of CDP-choline pathway genes rescues INO1 expression defect in scs2Δ cells. INO1 mRNA Northern blot; INO1 promoter-lacZ reporter; phospholipid composition analysis; genetic epistasis with CDP-choline pathway mutants Journal of biochemistry Medium 12761300
2004 Activation of INO1 (ISYNA1 ortholog) recruits the gene locus to the nuclear periphery; repressed INO1 is distributed throughout the nucleoplasm; recruitment requires the transcriptional activator Hac1p (produced upon UPR induction) and the integral membrane protein Scs2p (which antagonizes Opi1p repressor); artificial tethering of INO1 to the nuclear membrane enables activation in the absence of Scs2p. Fluorescence microscopy of GFP-tagged INO1 locus; genetic analysis of hac1Δ, scs2Δ, opi1Δ; artificial membrane tethering experiment PLoS biology High 15455074
2004 The UPR pathway plays a functional role in membrane trafficking under secretory stress; UPR loss-of-function (hac1Δ, ire1Δ) exacerbates secretory defects and slows vacuolar protein transport; high UPR induction under secretory stress does not correlate with elevated INO1 expression, indicating UPR and INO1 regulatory signals are separable. Carboxypeptidase Y transit time assay; genetic interaction analysis (Sec– mutations with ire1Δ/hac1Δ); INO1-lacZ reporter; UPR reporter Genetics Medium 15371354
2004 In Mycobacterium tuberculosis, four active-site residues of inositol-1-phosphate synthase (Ino1, homolog of ISYNA1) are essential for enzymatic activity; site-directed mutagenesis of these residues abolished activity; a D310N mutation caused loss of the active-site Zn²⁺ ion and a conformational change in the NAD⁺ cofactor; the ino1 gene is essential for mycobacterial growth and virulence. Site-directed mutagenesis of four active-site residues; enzyme activity assay; metal ion analysis; NAD⁺ cofactor conformational assessment; conditional knockout in macrophages and SCID mice Molecular microbiology Medium 14763976
2005 Snf1 kinase and Sit4 phosphatase have opposing roles in INO1 transcription: Snf1 promotes activation while Sit4 represses it; both regulate binding of TATA-binding protein (TBP) to the INO1 promoter as shown by chromatin immunoprecipitation; sit4 mutation suppresses snf1Δ inositol auxotrophy; TOR signaling (via rapamycin) reduces INO1 activation through Sit4. Chromatin immunoprecipitation (ChIP) for TBP at INO1 promoter; genetic suppressor analysis; rapamycin treatment; INO1-lacZ reporter Genetics High 15716495
2010 Interaction of a DNA 'zip code' (11-bp memory recruitment sequence, MRS) in the INO1 promoter with the nuclear pore complex (NPC) protein Nup100 controls both peripheral targeting of recently repressed INO1 and incorporation of histone variant H2A.Z; loss of MRS or Nup100 abolishes INO1 transcriptional memory, leading to nucleoplasmic localization and slower reactivation. Fluorescence microscopy of INO1 locus position; H2A.Z chromatin immunoprecipitation; promoter MRS deletion analysis; nup100Δ genetic analysis; reactivation kinetics assay Molecular cell High 20932479
2010 Complete derepression of INO1 transcription requires cooperative binding of both the Ino2p-Ino4p bHLH heterodimer to UAS(INO) sites in the INO1 promoter and Cbf1p binding to distal sites encompassing the upstream SNA3 ORF; Cbf1p binding requires prior Ino2p-Ino4p binding and vice versa; Cbf1p binding is required for recruitment of the ISW2 chromatin-remodeling complex to UAS(INO) sites. Chromatin immunoprecipitation (ChIP) for Cbf1p, Ino2p, Ino4p, and ISW2 at INO1 promoter; INO1-lacZ reporter in cbf1Δ, ino2Δ, ino4Δ, isw2Δ mutants Eukaryotic cell High 20935143
2011 Rat Isyna1 (myo-inositol-3-phosphate synthase gene) is regulated by DNA methylation in a tissue-specific manner; in vitro methylation of the promoter suppresses transcription; a specific CpG residue in the -700 to -500 bp region is required for promoter activity in neuronal cells; a tissue-specific differentially methylated region (T-DMR) between +450 and +650 bp correlates inversely with mRNA levels across tissues. Transfection with in vitro methylated promoter constructs; Southern blot with methylation-sensitive restriction enzyme; CpG methylation profiling; CpG mutation analysis by transfection Epigenomics Medium 21841945
2015 INO1 transcriptional memory involves interchromosomal clustering: during memory, both alleles of INO1 cluster together in diploids, and endogenous INO1 clusters with an ectopic copy in haploids; memory clustering requires Nup100 and two sets of DNA zip codes (those for active targeting and those for memory targeting); clustering is cell cycle-regulated during memory but peripheral localization is not. Fluorescence microscopy of tagged INO1 loci in diploid and haploid cells; genetic analysis of nup100Δ and zip code mutations; cell cycle staging Microbial cell (Graz, Austria) Medium 26688804
2016 Human ISYNA1 (inositol-3-phosphate synthase) is a direct transcriptional target of p53; p53 activates ISYNA1 expression through a p53 response element in the seventh exon; ectopic ISYNA1 expression increases intracellular myo-inositol levels and suppresses tumor cell growth; ISYNA1 knockdown causes resistance to adriamycin treatment, placing ISYNA1 downstream of p53 in growth suppression. Microarray screening followed by p53 induction; chromatin immunoprecipitation for p53 at ISYNA1 response element; myo-inositol measurement after ISYNA1 overexpression; cell proliferation assay; siRNA knockdown with drug treatment International journal of oncology High 27035231
2020 ISYNA1 acts as a tumor suppressor downstream of MSI2 (Musashi2) in pancreatic cancer; MSI2 represses ISYNA1 expression (dependent on wild-type p53); ISYNA1 silencing promotes cell proliferation and cell cycle progression by inhibiting p21, and enhances migration/invasion by upregulating ZEB-1; MSI2 silencing-induced suppression of migration is rescued by ISYNA1 knockdown, defining an MSI2→ISYNA1→p21/ZEB-1 pathway. siRNA knockdown and overexpression of ISYNA1 and MSI2; cell proliferation and cell cycle assays; migration/invasion assays; Western blot for p21 and ZEB-1; rescue experiments Journal of cellular and molecular medicine Medium 32779876
2022 INO1 transcriptional memory involves RNAPII-independent H3K4 dimethylation (H3K4me2) that is mitotically heritable; H3K4me2 at the INO1 locus requires Nup100, SET3C, and the Leo1 subunit of the Paf1 complex, but not RNAPII; upon loss of an essential transcription factor, this H3K4me2 is inherited through multiple cell cycles; COMPASS (the H3K4 methyltransferase) physically interacts with SET3C (the potential H3K4me2 reader), suggesting a spreading/re-incorporation mechanism. ChIP for H3K4me2 after RNAPII depletion; genetic analysis of nup100Δ, set3c, leo1Δ mutants; cell cycle tracking of histone mark inheritance; co-immunoprecipitation of COMPASS and SET3C eLife High 35579426

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 iPS cells produce viable mice through tetraploid complementation. Nature 563 19672241
2004 Gene recruitment of the activated INO1 locus to the nuclear membrane. PLoS biology 326 15455074
2014 iPS cells: a game changer for future medicine. The EMBO journal 299 24500035
2011 Small RNA-mediated regulation of iPS cell generation. The EMBO journal 246 21285944
2011 Proteomic and phosphoproteomic comparison of human ES and iPS cells. Nature methods 216 21983960
1986 Expression of the Saccharomyces cerevisiae inositol-1-phosphate synthase (INO1) gene is regulated by factors that affect phospholipid synthesis. Molecular and cellular biology 207 3025587
2014 iPS cell technologies: significance and applications to CNS regeneration and disease. Molecular brain 182 24685317
1994 INO2 and INO4 gene products, positive regulators of phospholipid biosynthesis in Saccharomyces cerevisiae, form a complex that binds to the INO1 promoter. The Journal of biological chemistry 169 8195172
2010 Interaction of a DNA zip code with the nuclear pore complex promotes H2A.Z incorporation and INO1 transcriptional memory. Molecular cell 160 20932479
2023 iPS-cell-derived microglia promote brain organoid maturation via cholesterol transfer. Nature 148 37914940
2020 iPS cell-based therapy for Parkinson's disease: A Kyoto trial. Regenerative therapy 142 33490319
2008 Retroviral vector silencing during iPS cell induction: an epigenetic beacon that signals distinct pluripotent states. Journal of cellular biochemistry 125 18773452
1997 Role of the yeast phosphatidylinositol/phosphatidylcholine transfer protein (Sec14p) in phosphatidylcholine turnover and INO1 regulation. The Journal of biological chemistry 116 9252414
1991 Analysis of sequences in the INO1 promoter that are involved in its regulation by phospholipid precursors. Nucleic acids research 116 2027776
2010 iPS cells: a source of cardiac regeneration. Journal of molecular and cellular cardiology 114 21040726
2023 Integrated intracellular organization and its variations in human iPS cells. Nature 103 36599983
1992 A dominant mutation that alters the regulation of INO1 expression in Saccharomyces cerevisiae. Journal of biochemistry 98 1587797
2001 Lithium and valproate decrease inositol mass and increase expression of the yeast INO1 and INO2 genes for inositol biosynthesis. The Journal of biological chemistry 97 11278273
2015 Modeling Alzheimer's disease with human induced pluripotent stem (iPS) cells. Molecular and cellular neurosciences 93 26657644
2019 Overview: an iPS cell stock at CiRA. Inflammation and regeneration 91 31497180
2001 Inhibition of acetyl coenzyme A carboxylase activity restores expression of the INO1 gene in a snf1 mutant strain of Saccharomyces cerevisiae. Molecular and cellular biology 90 11486011
2014 iPS cell technologies and cartilage regeneration. Bone 85 25026496
2013 Technological overview of iPS induction from human adult somatic cells. Current gene therapy 83 23320476
2008 From fibroblasts to iPS cells: induced pluripotency by defined factors. Journal of cellular biochemistry 81 18668528
2010 iPS cell technology in regenerative medicine. Annals of the New York Academy of Sciences 78 20392216
2004 The Mycobacterium tuberculosis ino1 gene is essential for growth and virulence. Molecular microbiology 77 14763976
2011 iPS cells to model CDKL5-related disorders. European journal of human genetics : EJHG 73 21750574
2009 Embryonic stem cell microRNAs: defining factors in induced pluripotent (iPS) and cancer (CSC) stem cells? Current stem cell research & therapy 71 19492978
1984 Isolation of the yeast INO1 gene: located on an autonomously replicating plasmid, the gene is fully regulated. Proceedings of the National Academy of Sciences of the United States of America 69 6374665
2018 Tumorigenicity-associated characteristics of human iPS cell lines. PloS one 64 30286143
1996 The role of phosphatidylcholine biosynthesis in the regulation of the INO1 gene of yeast. The Journal of biological chemistry 63 8810347
2004 Role of the unfolded protein response pathway in secretory stress and regulation of INO1 expression in Saccharomyces cerevisiae. Genetics 60 15371354
2017 Modelling IRF8 Deficient Human Hematopoiesis and Dendritic Cell Development with Engineered iPS Cells. Stem cells (Dayton, Ohio) 58 28090699
2017 Mechanism of human somatic reprogramming to iPS cell. Laboratory investigation; a journal of technical methods and pathology 51 28530648
2014 Primate iPS cells as tools for evolutionary analyses. Stem cell research 50 24631741
2002 Role of the unfolded protein response pathway in regulation of INO1 and in the sec14 bypass mechanism in Saccharomyces cerevisiae. Genetics 49 12242221
2015 Modeling Kidney Disease with iPS Cells. Biomarker insights 48 26740740
2005 The Snf1 protein kinase and Sit4 protein phosphatase have opposing functions in regulating TATA-binding protein association with the Saccharomyces cerevisiae INO1 promoter. Genetics 48 15716495
2000 Regulation of the yeast INO1 gene. The products of the INO2, INO4 and OPI1 regulatory genes are not required for repression in response to inositol. Genetics 48 10747047
2014 iPS cell derived neuronal cells for drug discovery. Trends in pharmacological sciences 47 25096281
2008 Induced pluripotent stem (iPS) cells as in vitro models of human neurogenetic disorders. Neurogenetics 47 18791750
1995 Cloning and sequence of the SCS2 gene, which can suppress the defect of INO1 expression in an inositol auxotrophic mutant of Saccharomyces cerevisiae. Journal of biochemistry 47 8537323
1981 Inositol Mutants of SACCHAROMYCES CEREVISIAE: Mapping the ino1 Locus and Characterizing Alleles of the ino1, ino2 and ino4 Loci. Genetics 47 17249096
2010 Gene-delivery systems for iPS cell generation. Expert opinion on biological therapy 46 20088717
2014 Induced pluripotent stem (iPS) cells: a new source for cell-based therapeutics? Journal of controlled release : official journal of the Controlled Release Society 45 24746625
2015 Using iPS Cells toward the Understanding of Parkinson's Disease. Journal of clinical medicine 44 26239346
2011 Safeguarding nonhuman primate iPS cells with suicide genes. Molecular therapy : the journal of the American Society of Gene Therapy 43 21587213
2008 iPS cells: a more critical review. Stem cells and development 41 18426340
2016 Regulation of myo-inositol biosynthesis by p53-ISYNA1 pathway. International journal of oncology 40 27035231
1999 Evidence for the involvement of the Glc7-Reg1 phosphatase and the Snf1-Snf4 kinase in the regulation of INO1 transcription in Saccharomyces cerevisiae. Genetics 39 10224244
2003 Role of the yeast VAP homolog, Scs2p, in INO1 expression and phospholipid metabolism. Journal of biochemistry 37 12761300
2018 Synthetic mRNAs Drive Highly Efficient iPS Cell Differentiation to Dopaminergic Neurons. Stem cells translational medicine 36 30387318
2001 The Saccharomyces cerevisiae Isw2p-Itc1p complex represses INO1 expression and maintains cell morphology. Journal of bacteriology 36 11489850
2019 Review: corneal endothelial cell derivation methods from ES/iPS cells. Inflammation and regeneration 31 31592286
2018 Modeling APC mutagenesis and familial adenomatous polyposis using human iPS cells. PloS one 31 30024920
2010 ES and iPS cell research for cardiovascular regeneration. Experimental cell research 31 20385126
2017 iPS cells in the study of PD molecular pathogenesis. Cell and tissue research 29 29234887
2013 Understanding telomere diseases through analysis of patient-derived iPS cells. Current opinion in genetics & development 29 23993228
2009 Reprogramming therapeutics: iPS cell prospects for neurodegenerative disease. Neuron 29 19217371
2010 Induced pluripotent stem (iPS) cell research overview. Cell transplantation 28 20887681
1996 Functional characterization of the repeated UASINO element in the promoters of the INO1 and CHO2 genes of yeast. Yeast (Chichester, England) 28 8810039
2021 SUR1-mutant iPS cell-derived islets recapitulate the pathophysiology of congenital hyperinsulinism. Diabetologia 27 33404684
2016 10th anniversary of iPS cells: the challenges that lie ahead. Journal of biochemistry 26 27387749
2012 Emerging methods for preparing iPS cells. Japanese journal of clinical oncology 26 22826352
2015 Myogenic Precursors from iPS Cells for Skeletal Muscle Cell Replacement Therapy. Journal of clinical medicine 24 26239126
2013 Disease-specific iPS cell models in neuroscience. Current molecular medicine 24 23642064
2009 Human iPS cell derivation/reprogramming. Current protocols in stem cell biology 24 19170021
2021 Epigenetic Memory: Lessons From iPS Cells Derived From Human β Cells. Frontiers in endocrinology 23 33584546
2014 iPS Cells for Modelling and Treatment of Retinal Diseases. Journal of clinical medicine 23 26237613
2020 Retention of Somatic Memory Associated with Cell Identity, Age and Metabolism in Induced Pluripotent Stem (iPS) Cells Reprogramming. Stem cell reviews and reports 21 32016780
2019 LIM homeobox 2 promotes interaction between human iPS-derived hepatic progenitors and iPS-derived hepatic stellate-like cells. Scientific reports 21 30765795
2012 Methods for iPS cell generation for basic research and clinical applications. Biotechnology journal 21 22378737
2020 Musashi2 promotes the progression of pancreatic cancer through a novel ISYNA1-p21/ZEB-1 pathway. Journal of cellular and molecular medicine 20 32779876
2014 Profiling the microRNA Expression in Human iPS and iPS-derived Retinal Pigment Epithelium. Cancer informatics 20 25392691
2013 Telomere reprogramming and maintenance in porcine iPS cells. PloS one 20 24098638
2012 The elite and stochastic model for iPS cell generation: multilineage-differentiating stress enduring (Muse) cells are readily reprogrammable into iPS cells. Cytometry. Part A : the journal of the International Society for Analytical Cytology 20 22693162
2012 Modeling long-QT syndromes with iPS cells. Journal of cardiovascular translational research 20 23076501
2024 iPS cell therapy 2.0: Preparing for next-generation regenerative medicine. BioEssays : news and reviews in molecular, cellular and developmental biology 19 38922935
2016 Induced Pluripotent Stem (iPS) Cell Culture Methods and Induction of Differentiation into Endothelial Cells. Methods in molecular biology (Clifton, N.J.) 19 25687301
2022 Mitotically heritable, RNA polymerase II-independent H3K4 dimethylation stimulates INO1 transcriptional memory. eLife 18 35579426
2015 INO1 transcriptional memory leads to DNA zip code-dependent interchromosomal clustering. Microbial cell (Graz, Austria) 18 26688804
2011 Differential methylation of the gene encoding myo-inositol 3-phosphate synthase (Isyna1) in rat tissues. Epigenomics 18 21841945
2002 Epi-inositol regulates expression of the yeast INO1 gene encoding inositol-1-P synthase. Molecular psychiatry 18 11840310
1999 The REG1 gene product is required for repression of INO1 and other inositol-sensitive upstream activating sequence-containing genes of yeast. Genetics 18 10224245
1994 Comparison of INO1 gene sequences and products in Candida albicans and Saccharomyces cerevisiae. Yeast (Chichester, England) 18 7975896
2021 A ROCK Inhibitor Promotes Graft Survival during Transplantation of iPS-Cell-Derived Retinal Cells. International journal of molecular sciences 17 33810153
2019 Expression regulation of myo-inositol 3-phosphate synthase 1 (INO1) in determination of phytic acid accumulation in rice grain. Scientific reports 17 31619750
2017 Treatment of Diabetes Mellitus Using iPS Cells and Spice Polyphenols. Journal of diabetes research 17 28758131
2013 Clinical grade iPS cells: need for versatile small molecules and optimal cell sources. Chemistry & biology 17 24267275
2020 Strategies for immune regulation in iPS cell-based cardiac regenerative medicine. Inflammation and regeneration 16 33005258
2011 DNA methylation assay for X-chromosome inactivation in female human iPS cells. Stem cell reviews and reports 16 21373884
2011 Recurrent trisomy and Robertsonian translocation of chromosome 14 in murine iPS cell lines. Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology 16 22009222
2010 Derepression of INO1 transcription requires cooperation between the Ino2p-Ino4p heterodimer and Cbf1p and recruitment of the ISW2 chromatin-remodeling complex. Eukaryotic cell 16 20935143
2021 Metabolomics and transcriptomics of pheromone biosynthesis in an aggressive forest pest Ips typographus. Insect biochemistry and molecular biology 15 34808354
2020 Ex vivo generation of platelet products from human iPS cells. Inflammation and regeneration 15 33292717
2016 Induced Pluripotent Stem (iPS) Cells in Dentistry: A Review. International journal of stem cells 15 27572712
2013 Induced pluripotent stem (iPS) cells from human fetal stem cells (hFSCs). Organogenesis 15 23823661
2011 Generation of clinically relevant "induced pluripotent stem" (iPS) cells. Journal of stem cells 15 23264997
1995 INO1-100: an allele of the Saccharomyces cerevisiae INO1 gene that is transcribed without the action of the positive factors encoded by the INO2, INO4, SWI1, SWI2 and SWI3 genes. Nucleic acids research 15 7753636
2023 Progress of iPS cell-based transplantation therapy for retinal diseases. Japanese journal of ophthalmology 14 36626080

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