Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have independently identified and DNA sequenced the INO2 locus by its close proximity to the KIN1 locus in Saccharomyces cerevisiae. Mutant strains in which the INO2 chromosomal locus has been deleted show pleiotropic phenotypes under growth conditions of inositol/choline availability. Many ino2 delta cells show delocalized cell growth resulting in large cells having aberrant shapes. These mutant cells may display nuclear segregation or positioning defects as well as defects in bud formation. Furthermore, homozygous ino2 delta-1 diploids fail to sporulate. Previous studies have shown that INO2 mutants are defective in phospholipid synthesis due to an inability to derepress the INO1 gene, the structural gene for inositol-1-phosphate synthase. To identify and determine the function of Ino2p in yeast cells, we raised antibodies to a beta-galactosidase/Ino2 fusion protein. The INO2 open reading frame codes for a 304 amino acid protein with a calculated molecular weight of 39.7 kDa. Immunoblot analysis reveals two Ino2-specific proteins of approximately 44 and 46 kDa. The 44 kDa species is localized to the nucleus. Ino2p is believed to function as a positive transcriptional activator in phospholipid synthesis. Our results suggest that it affects additional pathways important to polarized cell growth and division perhaps by functioning as a more general transcriptional factor.
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PMID:INO2, a regulatory gene in yeast phospholipid biosynthesis, affects nuclear segregation and bud pattern formation. 801 48

The Ume6p-Sin3p-Rpd3p complex negatively regulates expression of genes containing a Ume6p binding site. However, these regulatory proteins also function independently to regulate gene expression both negatively and positively. The model system for this combinatorial regulation is the yeast phospholipid biosynthetic pathway. Sin3p negatively regulates the INO1, CHO1, CHO2 and OPI3 genes while Ume6p negatively regulates the INO1 gene and positively regulates the other genes. We have suggested that the positive regulation results from indirect effects on expression of the INO2 transcriptional activator gene. Here, we demonstrate that the effect of Ume6p on INO2 gene expression is also indirect. We also show that Rpd3p is a negative regulator of phospholipid biosynthetic gene expression. The ability of Ume6p, Sin3p and Rpd3p to differentially regulate expression of the phospholipid biosynthetic genes affects phospholipid composition. A sin3 mutant strain lacks detectable levels of phosphatidylethanolamine and elevated levels of phosphatidylcholine (PC) and a rpd3 mutant strain has reduced levels of PC. These alterations in membrane composition suggest that there may exist additional differences in regulation of phospholipid biosynthetic gene expression and that membrane compositions may be coordinated with other biological processes regulated by Ume6p, Sin3p and Rpd3p.
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PMID:Combinatorial regulation of phospholipid biosynthetic gene expression by the UME6, SIN3 and RPD3 genes. 1093 32

The yeast INO2 gene encodes a transcriptional activator. Inositol and choline repress transcription of the INO2 gene, and its target genes. That is, INO2 transcription is auto-regulated. This observation prompted two separate investigations to determine if regulation of INO2 is required for regulation of its target genes. One study, using northern blot hybridization, showed that constitutive INO2 transcription did not affect regulation of the INO1 gene, while another study revealed that it severely dampened regulation of an INO1-lacZ gene. By repeating both assays from a single yeast strain we demonstrate that this disparity is due to the different reporter systems.
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PMID:Over-expression of the INO2 regulatory gene alters regulation of an INO1-lacZ reporter gene but does not affect regulation of INO1 expression. 1140 99

In the de novo synthesis of inositol, the conversion of D-glucose-6-phosphate to L-myo-inositol-1-phosphate (MIP) is catalyzed by MIP synthase. Little is known about mammalian MIP synthase and nothing is known about its regulation. The second step in inositol biosynthesis is the conversion of MIP to inositol by inositol-monophosphatase (IMPase), a common step to inositol production via the de novo pathway and its recycling from inositol phosphates. Because lithium inhibits IMPase both in yeast and in mammals, and the drug upregulates yeast MIP synthase (INO1) and downregulates IMPase (INM1), the present study was undertaken to determine whether chronic in vivo therapeutic lithium concentrations affect MIP synthase and IMPase expression in mouse frontal cortex and hippocampus. Mice were treated with food containing LiCl (2.5 g/kg) for 10 days. RNA was purified from the brain areas and mRNA amplified using RT-PCR. Expression of MIP synthase and IMPA1 (one of the genes coding for IMPase) but not IMPA2 was upregulated in mouse hippocampus. None of the genes were affected in the frontal cortex. In yeast, when inositol is limiting, the heterodimeric transcriptional activator Ino2p/Ino4p derepresses expression of INO1 by binding to the upstream activation sequence UAS(INO). Using the TFSEARCH program, we found that the promoter of the virtual human MIP synthase gene contains upstream stimulating factor (USF) elements with a similar core binding sequence. The fact that lithium treatment upregulates both MIP synthase and IMPA1 mRNA levels in mouse hippocampus may reflect a compensatory response of both genes to inositol depletion.
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PMID:The effect of lithium on expression of genes for inositol biosynthetic enzymes in mouse hippocampus; a comparison with the yeast model. 1287 81

The spatial arrangement of chromatin within the nucleus can affect reactions that occur on the DNA and is likely to be regulated. Here we show that activation of INO1 occurs at the nuclear membrane and requires the integral membrane protein Scs2. Scs2 antagonizes the action of the transcriptional repressor Opi1 under conditions that induce the unfolded protein response (UPR) and, in turn, activate INO1. Whereas repressed INO1 localizes throughout the nucleoplasm, the gene is recruited to the nuclear periphery upon transcriptional activation. Recruitment requires the transcriptional activator Hac1, which is produced upon induction of the UPR, and is constitutive in a strain lacking Opi1. Artificial recruitment of INO1 to the nuclear membrane permits activation in the absence of Scs2, indicating that the intranuclear localization of a gene can profoundly influence its mechanism of activation. Gene recruitment to the nuclear periphery, therefore, is a dynamic process and appears to play an important regulatory role.
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PMID:Gene recruitment of the activated INO1 locus to the nuclear membrane. 1545 74

Mat formation in the bakers' yeast Saccharomyces cerevisiae is a surface-associated phenomenon in which yeast cells spread over the surface of a low-density agar petri plate as a complex film. This spreading growth occurs by sliding motility and is dependent on the adhesion protein (adhesin) Flo11p. In order to identify molecular pathways that govern mat formation, whole-genome transcriptional profiling was used to compare cells growing as a mat to cells growing in a suspension culture (planktonic cells). This analysis revealed that S. cerevisiae upregulates a subset of genes in response to growth on a surface. These genes included the INO1 gene, which encodes the myo-inositol-1-phosphate synthase, which carries out the rate-limiting step in inositol biosynthesis. Further inquiry revealed that a transcription factor that controls INO1 expression, called Opi1p, participates in the regulation of mat formation. Opi1p appears to modulate mat formation by influencing the expression of FLO11. The opi1Delta mutant was found to exhibit reduced FLO11 levels. Consequently, the opi1Delta mutant perturbs the FLO11-dependent phenotype of invasive growth. The opi1Delta mutant's defects in mat formation and invasive growth are dependent on the transcriptional activator Ino2p. These results indicate that Opi1p affects mat formation and invasive growth by participating in the regulation of FLO11.
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PMID:The Opi1p transcription factor affects expression of FLO11, mat formation, and invasive growth in Saccharomyces cerevisiae. 1689 11

Yeast Ino2p-Ino4p heterodimeric complex is well known as a transcriptional activator for the genes regulated by inositol and choline, such as the INO1 gene. Apl2p is a large subunit of the yeast adaptin complex, an adaptor complex required for the clathrin coat to bind to the membrane. We found that Ino2p, Ino4p, and Apl2p form a ternary complex. This interaction was initially observed in a yeast two-hybrid study and subsequently verified by co-immunoprecipitation. Ino2p and Ino4p bind to Apl2p in the same region of Apl2p, viz., at the middle part and the C-terminal part. Ino2p and Ino4p bind to Apl2p independently, but more strongly when both are present. Furthermore, a disruption of APL2 together with INO2 or INO4 rendered yeast cells sensitive to oxidative stress. INO2-APL2 double disruptants also showed growth inability in non-fermentable carbon sources, such as glycerol. These results indicate a genetic interaction between APL2, INO2 and INO4 and uncovere novel functions of the Ino2p-Ino4p-Apl2p complex in yeast.
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PMID:Ternary complex formation of Ino2p-Ino4p transcription factors and Apl2p adaptin beta subunit in yeast. 1709 Sep 27

ETR101, a human homolog of rat pip92, is a cellular immediate early gene induced by extracellular stimuli such as serum growth factors. ETR101 encodes a short-lived, proline-rich protein (ETR101) exhibiting no significant sequence similarity to any other known protein, and little is known about its function. We investigated the functioning of ETR101 as a transcriptional activator for the gene ISYNA1, which encodes human inositol 1-phosphate synthase. We constructed a yeast strain in which the chromosomal region of the PSS1 promoter was replaced with the human ISYNA1 promoter. Using this yeast strain, we screened human cDNAs, which activated the ISYNA1 promoter, and thus expressed the PSS1 as a reporter gene. We obtained two types of cDNA, E2F1, known as a gene encoding Rb-binding protein, and ETR101. The E2F1 gene product (E2F1) is known to bind to and activate the ISYNA1 promoter. In a manner similar to E2F1, ETR101 binds to and activates the ISYNA1 promoter.
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PMID:Functional analyses of immediate early gene ETR101 expressed in yeast. 1958 37

The relationship between histone acetylation and transcriptional activation at the yeast INO1 gene was addressed. INO1 encodes a key enzyme required for the de novo synthesis of phosphatidylinositol. Induction of INO1 resulted in acetylation of both histones H3 and H4 at the INO1 promoter and sequences farther downstream in the coding region, suggesting a gene-wide acetylation in response to transcriptional activation. Such chromatin remodeling activity requires the presence of transcriptional activator Ino2p. This indicates that histone acetylation is an activator-dependent event. Furthermore, the increase of histone acetylation is due to the increase of acetylation levels per nucleosome rather than the increase of nucleosome density. Therefore, these observations constitute evidence for the molecular mechanism of the correlation between histone acetylation and INO1 activity.
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PMID:Gene-wide histone acetylation at the yeast INO1 requires the transcriptional activator Ino2p. 2001 75

Transcriptional co-activators contribute to gene expression through different mechanisms. We used various biochemical tools available for Saccharomyces cerevisiae to examine the mechanism of INO1 expression. INO1 encodes inositol-3-phosphate synthase, which catalyzes the rate-limiting step in the synthesis of inositol, a key player in phospholipid biosynthesis. Herein, we had demonstrated that the recruitment of histone acetylases Gcn5p and Esa1p mainly relied on the presence of transcriptional activator Ino2p during INO1 activation. However, the presence of the chromatin remodelers, Ino80p and Snf2p, may contribute to the additive effect of Gcn5p recruitment. We also showed that the recruitment of chromatin remodelers, Ino80p and Snf2p, is independent of the presence of histone acetylases. Furthermore, INO1 expression can be activated exclusively by the activator and chromatin remodelers, suggesting a dispensable role of histone acetylases in INO1 induction. Therefore, our data provide a mechanism for cross talk within transcriptional co-activators during INO1 activation.
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PMID:INO1 induction requires chromatin remodelers Ino80p and Snf2p but not the histone acetylases. 2228 92


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