scholarly journals MOT2 encodes a negative regulator of gene expression that affects basal expression of pheromone-responsive genes in Saccharomyces cerevisiae.

1994 ◽  
Vol 14 (5) ◽  
pp. 3139-3149 ◽  
Author(s):  
R M Cade ◽  
B Errede
Keyword(s):  
Gene Expression ◽  
Saccharomyces Cerevisiae ◽  
Protein Kinases ◽  
Signal Transmission ◽  
Negative Regulator ◽  
Specific Gene ◽  
Deletion Mutants ◽  
Basal Expression ◽  
Regulatory Effects ◽  
Induced Signal

Pheromones induce haploid cells of Saccharomyces cerevisiae to differentiate into a mating-competent state. Ste11p is one of several protein kinases required to transmit the pheromone-induced signal and to maintain basal expression of certain mating-specific genes in the absence of pheromone stimulation. To identify potential regulators of Ste11p, we screened for suppressors that restored mating and basal transcriptional competence to a strain with a conditionally functional Ste11p. This screen uncovered a novel gene we call MOT2, for modulator of transcription. A mot2 deletion mutation leads to modest increases in the basal amounts of mRNA for several pheromone-responsive genes. Yet mot2 deletion does not affect the signal transmission activity of the pathway in either the presence or absence of pheromone stimulation. Therefore, we propose that Mot2p, directly or indirectly, represses basal transcription of certain mating-specific genes. Because mot2 deletion mutants also have a conditional cell lysis phenotype, we expect that Mot2p regulatory effects may be more global than for mating-specific gene expression.

scholarly journals Pheromone-induced signal transduction in Saccharomyces cerevisiae requires the sequential function of three protein kinases.

1993 ◽  
Vol 13 (4) ◽  
pp. 2069-2080 ◽  
Author(s):  
Z Zhou ◽  
A Gartner ◽  
R Cade ◽  
G Ammerer ◽  
B Errede
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Signal Transduction ◽  
Protein Kinases ◽  
Signal Transmission ◽  
Yeast Cells ◽  
In Vitro Assays ◽  
Induced Signal ◽  
Hyperphosphorylated Form ◽  
Dependent Mechanism

Protein phosphorylation plays an important role in pheromone-induced differentiation processes of haploid yeast cells. Among the components necessary for signal transduction are the STE7 and STE11 kinases and either one of the redundant FUS3 and KSS1 kinases. FUS3 and presumably KSS1 are phosphorylated and activated during pheromone induction by a STE7-dependent mechanism. Pheromone also induces the accumulation of STE7 in a hyperphosphorylated form. This modification of STE7 requires the STE11 kinase, which is proposed to act before STE7 during signal transmission. Surprisingly, STE7 hyperphosphorylation also requires a functional FUS3 (or KSS1) kinase. Using in vitro assays for FUS3 phosphorylation, we show that pheromone activates STE7 even in the absence of FUS3 and KSS1. Therefore, STE7 activation must precede modification of FUS3 (and KSS1). These findings suggest that STE7 hyperphosphorylation is a consequence of its activation but not the determining event.

scholarly journals Pheromone-induced signal transduction in Saccharomyces cerevisiae requires the sequential function of three protein kinases

1993 ◽  
Vol 13 (4) ◽  
pp. 2069-2080
Author(s):  
Z Zhou ◽  
A Gartner ◽  
R Cade ◽  
G Ammerer ◽  
B Errede
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Signal Transduction ◽  
Protein Kinases ◽  
Signal Transmission ◽  
Yeast Cells ◽  
In Vitro Assays ◽  
Induced Signal ◽  
Hyperphosphorylated Form ◽  
Dependent Mechanism

Protein phosphorylation plays an important role in pheromone-induced differentiation processes of haploid yeast cells. Among the components necessary for signal transduction are the STE7 and STE11 kinases and either one of the redundant FUS3 and KSS1 kinases. FUS3 and presumably KSS1 are phosphorylated and activated during pheromone induction by a STE7-dependent mechanism. Pheromone also induces the accumulation of STE7 in a hyperphosphorylated form. This modification of STE7 requires the STE11 kinase, which is proposed to act before STE7 during signal transmission. Surprisingly, STE7 hyperphosphorylation also requires a functional FUS3 (or KSS1) kinase. Using in vitro assays for FUS3 phosphorylation, we show that pheromone activates STE7 even in the absence of FUS3 and KSS1. Therefore, STE7 activation must precede modification of FUS3 (and KSS1). These findings suggest that STE7 hyperphosphorylation is a consequence of its activation but not the determining event.

scholarly journals Genetic influences on cell type specific gene expression and splicing during neurogenesis elucidate regulatory mechanisms of brain traits

2020 ◽  
Author(s):  
Nil Aygün ◽  
Angela L. Elwell ◽  
Dan Liang ◽  
Michael J. Lafferty ◽  
Kerry E. Cheek ◽  
...  
Keyword(s):  
Gene Expression ◽  
Regulatory Elements ◽  
Regulatory Mechanisms ◽  
Specific Gene ◽  
Cell Type ◽  
Specific Expression ◽  
Risk Variants ◽  
Allele Specific ◽  
Cell Type Specific ◽  
Regulatory Effects

SummaryInterpretation of the function of non-coding risk loci for neuropsychiatric disorders and brain-relevant traits via gene expression and alternative splicing is mainly performed in bulk post-mortem adult tissue. However, genetic risk loci are enriched in regulatory elements of cells present during neocortical differentiation, and regulatory effects of risk variants may be masked by heterogeneity in bulk tissue. Here, we map e/sQTLs and allele specific expression in primary human neural progenitors (n=85) and their sorted neuronal progeny (n=74). Using colocalization and TWAS, we uncover cell-type specific regulatory mechanisms underlying risk for these traits.

Positive control of sporulation-specific genes by the IME1 and IME2 products in Saccharomyces cerevisiae

1990 ◽  
Vol 10 (5) ◽  
pp. 2104-2110
Author(s):  
A P Mitchell ◽  
S E Driscoll ◽  
H E Smith
Keyword(s):  
Gene Expression ◽  
Saccharomyces Cerevisiae ◽  
Meiotic Recombination ◽  
Positive Control ◽  
Spore Formation ◽  
Specific Gene ◽  
Heterologous Promoter ◽  
Yeast Saccharomyces Cerevisiae ◽  
Specific Gene Expression ◽  
Rapid Induction

In the yeast Saccharomyces cerevisiae, meiosis and spore formation require the induction of sporulation-specific genes. Two genes are thought to activate the sporulation program: IME1 and IME2 (inducer of meiosis). Both genes are induced upon entry into meiosis, and IME1 is required for IME2 expression. We report here that IME1 is essential for expression of four sporulation-specific genes. In contrast, IME2 is not absolutely essential for expression of the sporulation-specific genes, but contributes to their rapid induction. Expression of IME2 from a heterologous promoter permits the expression of these sporulation-specific genes, meiotic recombination, and spore formation in the absence of IME1. We propose that the IME1 and IME2 products can each activate sporulation-specific genes independently. In addition, the IME1 product stimulates sporulation-specific gene expression indirectly through activation of IME2 expression.

scholarly journals Sum1 and Hst1 repress middle sporulation-specific gene expression during mitosis in Saccharomyces cerevisiae

1999 ◽  
Vol 18 (22) ◽  
pp. 6448-6454 ◽  
Author(s):  
Jianxin Xie ◽  
Michael Pierce ◽  
Valérie Gailus-Durner ◽  
Marisa Wagner ◽  
Edward Winter ◽  
...  
Keyword(s):  
Gene Expression ◽  
Saccharomyces Cerevisiae ◽  
Specific Gene ◽  
Specific Gene Expression

scholarly journals Role of IME1 expression in regulation of meiosis in Saccharomyces cerevisiae.

1990 ◽  
Vol 10 (12) ◽  
pp. 6103-6113 ◽  
Author(s):  
H E Smith ◽  
S S Su ◽  
L Neigeborn ◽  
S E Driscoll ◽  
A P Mitchell
Keyword(s):  
Gene Expression ◽  
Saccharomyces Cerevisiae ◽  
Amino Acid ◽  
Specific Gene ◽  
Alpha Cells ◽  
Cell Type ◽  
Yeast Saccharomyces Cerevisiae ◽  
Specific Gene Expression ◽  
Gal1 Promoter ◽  
Acid Protein

Two signals are required for meiosis and spore formation in the yeast Saccharomyces cerevisiae: starvation and the MAT products a1 and alpha 2, which determine the a/alpha cell type. These signals lead to increased expression of the IME1 (inducer of meiosis) gene, which is required for sporulation and sporulation-specific gene expression. We report here the sequence of the IME1 gene and the consequences of IME1 expression from the GAL1 promoter. The deduced IME1 product is a 360-amino-acid protein with a tyrosine-rich C-terminal region. Expression of PGAL1-IME1 in vegetative a/alpha cells led to moderate accumulation of four early sporulation-specific transcripts (IME2, SPO11, SPO13, and HOP1); the transcripts accumulated 3- to 10-fold more after starvation. Two sporulation-specific transcripts normally expressed later (SPS1 and SPS2) did not accumulate until PGAL1-IME1 strains were starved, and the intact IME1 gene was not activated by PGAL1-IME1 expression. In a or alpha cells, which lack alpha 2 or a1, expression of PGAL1-IME1 led to the same pattern of IME2 and SPO13 expression as in a/alpha cells, as measured with ime2::lacZ and spo13::lacZ fusions. Thus, in wild-type strains, the increased expression of IME1 in starved a/alpha cells can account entirely for cell type control, but only partially for nutritional control, of early sporulation-specific gene expression. PGAL1-IME1 expression did not cause growing cells to sporulate but permitted efficient sporulation of amino acid-limited cells, which otherwise sporulated poorly. We suggest that IME1 acts primarily as a positive regulator of early sporulation-specific genes and that growth arrest is an independent prerequisite for execution of the sporulation program.

scholarly journals NDT80 and the Meiotic Recombination Checkpoint Regulate Expression of Middle Sporulation-Specific Genes in Saccharomyces cerevisiae

1998 ◽  
Vol 18 (10) ◽  
pp. 5750-5761 ◽  
Author(s):  
Shelley R. Hepworth ◽  
Helena Friesen ◽  
Jacqueline Segall
Keyword(s):  
Gene Expression ◽  
Saccharomyces Cerevisiae ◽  
Meiotic Recombination ◽  
Active Form ◽  
Specific Gene ◽  
Subsequent Generation ◽  
Genes Encoding ◽  
Recombination Checkpoint ◽  
Sporulation Genes ◽  
Meiosis I

ABSTRACT Distinct classes of sporulation-specific genes are sequentially expressed during the process of spore formation in Saccharomyces cerevisiae. The transition from expression of early meiotic genes to expression of middle sporulation-specific genes occurs at about the time that cells exit from pachytene and form the meiosis I spindle. To identify genes encoding potential regulators of middle sporulation-specific gene expression, we screened for mutants that expressed early meiotic genes but failed to express middle sporulation-specific genes. We identified mutant alleles ofRPD3, SIN3, and NDT80 in this screen. Rpd3p, a histone deacetylase, and Sin3p are global modulators of gene expression. Ndt80p promotes entry into the meiotic divisions. We found that entry into the meiotic divisions was not required for activation of middle sporulation genes; these genes were efficiently expressed in a clb1 clb3 clb4 strain, which fails to enter the meiotic divisions due to reduced Clb-dependent activation of Cdc28p kinase. In contrast, middle sporulation genes were not expressed in a dmc1 strain, which fails to enter the meiotic divisions because a defect in meiotic recombination leads to aRAD17-dependent checkpoint arrest. Expression of middle sporulation genes, as well as entry into the meiotic divisions, was restored to a dmc1 strain by mutation of RAD17. Our studies also revealed that NDT80 was a temporally distinct, pre-middle sporulation gene and that its expression was reduced, but not abolished, on mutation of DMC1,RPD3, SIN3, or NDT80 itself. In summary, our data indicate that Ndt80p is required for expression of middle sporulation genes and that the activity of Ndt80p is controlled by the meiotic recombination checkpoint. Thus, middle genes are expressed only on completion of meiotic recombination and subsequent generation of an active form of Ndt80p.

scholarly journals Phosphatidylinositol 3-Kinase Is a Negative Regulator of Cellular Differentiation

1997 ◽  
Vol 137 (5) ◽  
pp. 1127-1136 ◽  
Author(s):  
Andrzej Ptasznik ◽  
Gillian M. Beattie ◽  
Martin I. Mally ◽  
Vincenzo Cirulli ◽  
Ana Lopez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cellular Differentiation ◽  
Precursor Cells ◽  
Negative Regulator ◽  
Specific Gene ◽  
Phosphatidylinositol 3 Kinase ◽  
Specific Gene Expression ◽  
Endocrine Differentiation ◽  
Pi3k Activity ◽  
Phosphatidylinositol 3

Phosphatidylinositol 3-kinase (PI3K) has been shown to be an important mediator of intracellular signal transduction in mammalian cells. We show here, for the first time, that the blockade of PI3K activity in human fetal undifferentiated cells induced morphological and functional endocrine differentiation. This was associated with an increase in mRNA levels of insulin, glucagon, and somatostatin, as well as an increase in the insulin protein content and secretion in response to secretagogues. Blockade of PI3K also increased the proportion of pluripotent precursor cells coexpressing multiple hormones and the total number of terminally differentiated cells originating from these precursor cells. We examined whether any of the recently described modulators of endocrine differentiation could participate in regulating PI3K activity in fetal islet cells. The activity of PI3K was inversely correlated with the hepatocyte growth factor/scatter factor–induced downregulation or nicotinamideinduced upregulation of islet-specific gene expression, giving support to the role of PI3K, as a negative regulator of endocrine differentiation. In conclusion, our results provide a mechanism for the regulation of hormone-specific gene expression during human fetal neogenesis. They also suggest a novel function for PI3K, as a negative regulator of cellular differentiation.

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