Saccharomyces cerevisiae
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ABSTRACT:
PROVIDER: PRJNA144931 | ENA |
REPOSITORIES: ENA
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Project description:The FAR1 gene encodes a large protein, whose major function is inhibition of cyclin-dependent kinase complexes involved in the G1/S transition. It has been proposed that Far1, together with the G1 cyclin Cln3, may be part of a cell sizer mechanism that controls the entry into S phase. A genome-wide transcriptional analysis of FAR1-overexpressing and far1 deleted cells grown in ethanol- or glucose-supplemented minimal media indicates that FAR1 overexpression induces strong transcriptional remodelling, metabolism being the most affected cellular property. These data suggest that the Far1/Cln3 sizer regulates cell growth either directly or indirectly by affecting metabolism and pathways known to modulate ribosome biogenesis. A crucial role in mediating the effect of Far1 overexpression is played by the Sfp1 protein, a key transcriptional regulator of ribosome biogenesis, whose presence is mandatory to allow a coordinated increase in both RNA and protein levels in ethanol-grown cells.
2011-09-29 | GSE31143 | GEO
Project description:The FAR1 gene encodes a large protein, whose major function is inhibition of cyclin-dependent kinase complexes involved in the G1/S transition. It has been proposed that Far1, together with the G1 cyclin Cln3, may be part of a cell sizer mechanism that controls the entry into S phase. A genome-wide transcriptional analysis of FAR1-overexpressing and far1 deleted cells grown in ethanol- or glucose-supplemented minimal media indicates that FAR1 overexpression induces strong transcriptional remodelling, metabolism being the most affected cellular property. These data suggest that the Far1/Cln3 sizer regulates cell growth either directly or indirectly by affecting metabolism and pathways known to modulate ribosome biogenesis. A crucial role in mediating the effect of Far1 overexpression is played by the Sfp1 protein, a key transcriptional regulator of ribosome biogenesis, whose presence is mandatory to allow a coordinated increase in both RNA and protein levels in ethanol-grown cells. The experimental plan was designed to study the effect of alteration of dosage of the FAR1 gene on the transcriptional pattern of cells exponentially growing in media supplemented with either glucose or ethanol as a carbon source. To this end wild type cells (strain W303-1A), far1 deleted mutant (background W303-1A, relevant genotype far1::his3) and strain overexpressing FAR1 (background W303-1A, transformed with plasmid pTet-FAR1-15Myc (Alberghina et al., 2004)) were collected in independent triplicates in exponential growth as detailed in growth protocol. Microarray experiments were performed using a yeast S98 chip oligonucleotide array (Affymetrix, Inc.) according to the manufacturer's instructions (http://www.affymetrix.com/support/technical/manuals.affx).
2011-09-28 | E-GEOD-31143 | biostudies-arrayexpress
Project description:In Saccharomyces cerevisiae growth, size control and cell cycle progression are strictly coordinated and regulated according to the nutritional conditions. In particular, ribosome biogenesis appears a key event in this regulatory network. SFP1 encodes a zinc-finger protein promoting the transcription of a large cluster of genes involved in ribosome biogenesis. It has been suggested that Sfp1 is a cell size modulator acting at Start. To better study the regulatory role of Sfp1 and its putative involvement in cell size and cycle control, we analysed the behaviour of an sfp1 null mutant strain and of an isogenic reference strain growing in chemostat cultures. This approach allowed us to analyze both strains at the same specific growth rate, thus eliminating the secondary effects due to the slow growing phenotype that the sfp1 null mutant shows in shake flask. We studied glucose(anaerobic)- and ethanol(aerobic)-limited cultures, as paradigms of two different metabolic states. Major alterations of the transcriptional profile were observed during growth on glucose, while no significant differences were observed when comparing ethanol growing cultures. In particular, in the former growth condition, Sfp1 appears involved in the control of ribosome biogenesis but not of ribosomal protein gene expression. Experiment Overall Design: The reference S. cerevisiae strain CEN.PK113.7D and the isogenic sfp1 null mutant were grown in chemostat cultures under ethanol(aerobic)- and glucose(anaerobic)- limitation. The dilution rate was set at 0.10 h-1 and 0.05 h-1 for ethanol- and glucose-limited cultures, respectively. A genome-wide transcriptional analysis was performed for the reference and the sfp1 null mutant strains for each growth condition. All data presented in this work were derived from three independent chemostat cultures (12 samples in total were analysed).
2008-06-13 | E-GEOD-5238 | biostudies-arrayexpress
Project description:In Saccharomyces cerevisiae growth, size control and cell cycle progression are strictly coordinated and regulated according to the nutritional conditions. In particular, ribosome biogenesis appears a key event in this regulatory network. SFP1 encodes a zinc-finger protein promoting the transcription of a large cluster of genes involved in ribosome biogenesis. It has been suggested that Sfp1 is a cell size modulator acting at Start. To better study the regulatory role of Sfp1 and its putative involvement in cell size and cycle control, we analysed the behaviour of an sfp1 null mutant strain and of an isogenic reference strain growing in chemostat cultures. This approach allowed us to analyze both strains at the same specific growth rate, thus eliminating the secondary effects due to the slow growing phenotype that the sfp1 null mutant shows in shake flask. We studied glucose(anaerobic)- and ethanol(aerobic)-limited cultures, as paradigms of two different metabolic states. Major alterations of the transcriptional profile were observed during growth on glucose, while no significant differences were observed when comparing ethanol growing cultures. In particular, in the former growth condition, Sfp1 appears involved in the control of ribosome biogenesis but not of ribosomal protein gene expression. Keywords: global transcriptional profile, genetic modification, ribosome biogenesis
2007-11-10 | GSE5238 | GEO
Project description:Inactivation of theVHLtumor suppressor gene stabilizes HIF2a, which drives clear cell renal carcinoma (ccRCC). The HIF2ainhibitor belzutifan is approved for ccRCC treatment, butde novoand acquiredresistance are common. HIF2a, bound to ARNT, transcriptionally activates hundreds of genes. We performed genome-wide CRISPRa screens in HIF2a-dependent ccRCC lines treated with the belzutifan tool compound PT2399 to identify HIF2a-responsive genes that confer belzutifan resistance when not downregulated. Sustaining the expression of the HIF2atarget geneCCND1, encoding Cyclin D1, promoted HIF2a-independence/belzutifan resistance. This activity requires Cdk4/6 activation by Cyclin D1, but is not solely due to inhibitory phosphorylation of the canonical Cyclin D1 target, pRB. Indeed, ccRCC lines lacking all three pRB family members remained at least partially HIF2a-dependent. In this context. However, kinase-defective Cyclin D1 variants at least partially overrode belzutifan’s antiproliferative effects, suggesting that ccRCC promotion by Cyclin D1 requires the phosphorylation of pRB paralogs and one or more kinase-independent Cyclin D1 activities.
2025-03-20 | GSE277045 | GEO
Project description:Inactivation of theVHLtumor suppressor gene stabilizes HIF2a, which drives clear cell renal carcinoma (ccRCC). The HIF2ainhibitor belzutifan is approved for ccRCC treatment, butde novoand acquiredresistance are common. HIF2a, bound to ARNT, transcriptionally activates hundreds of genes. We performed genome-wide CRISPRa screens in HIF2a-dependent ccRCC lines treated with the belzutifan tool compound PT2399 to identify HIF2a-responsive genes that confer belzutifan resistance when not downregulated. Sustaining the expression of the HIF2atarget geneCCND1, encoding Cyclin D1, promoted HIF2a-independence/belzutifan resistance. This activity requires Cdk4/6 activation by Cyclin D1, but is not solely due to inhibitory phosphorylation of the canonical Cyclin D1 target, pRB. Indeed, ccRCC lines lacking all three pRB family members remained at least partially HIF2a-dependent. In this context. However, kinase-defective Cyclin D1 variants at least partially overrode belzutifan’s antiproliferative effects, suggesting that ccRCC promotion by Cyclin D1 requires the phosphorylation of pRB paralogs and one or more kinase-independent Cyclin D1 activities.
2025-03-20 | GSE277044 | GEO
Project description:Inactivation of theVHLtumor suppressor gene stabilizes HIF2a, which drives clear cell renal carcinoma (ccRCC). The HIF2ainhibitor belzutifan is approved for ccRCC treatment, butde novoand acquiredresistance are common. HIF2a, bound to ARNT, transcriptionally activates hundreds of genes. We performed genome-wide CRISPRa screens in HIF2a-dependent ccRCC lines treated with the belzutifan tool compound PT2399 to identify HIF2a-responsive genes that confer belzutifan resistance when not downregulated. Sustaining the expression of the HIF2atarget geneCCND1, encoding Cyclin D1, promoted HIF2a-independence/belzutifan resistance. This activity requires Cdk4/6 activation by Cyclin D1, but is not solely due to inhibitory phosphorylation of the canonical Cyclin D1 target, pRB. Indeed, ccRCC lines lacking all three pRB family members remained at least partially HIF2a-dependent. In this context. However, kinase-defective Cyclin D1 variants at least partially overrode belzutifan’s antiproliferative effects, suggesting that ccRCC promotion by Cyclin D1 requires the phosphorylation of pRB paralogs and one or more kinase-independent Cyclin D1 activities.
2025-03-20 | GSE277043 | GEO
Project description:RNAP II is frequently paused near gene promoters in mammals and its transition to productive elongation requires active recruitment of P-TEFb, a cyclin-dependent kinase for RNAP II and other key transcription elongation factors. A fraction of P-TEFb is sequestered in an inhibitory complex containing the 7SK noncoding RNA, but it has been unclear how P-TEFb is switched from the 7SK complex to RNAP II during transcription activation. We report that SRSF2 (also known as SC35, an SR splicing factor) is part of the 7SK complex assembled at gene promoters and plays a direct role in transcription pause release. We demonstrate RNA-dependent, coordinated release of SRSF2 and P-TEFb from the 7SK complex and transcription activation via SRSF2 binding to promoter-associated nascent RNA. These findings reveal an unanticipated SR protein function, a role for promoter-proximal nascent RNA in gene activation, and an analogous mechanism to HIV Tat/TAR for activating cellular genes. SR ChIP-seq, Pol II ChIP-seq, and Gro-seq
2013-05-09 | E-GEOD-45517 | biostudies-arrayexpress
Project description:Eukaryotic gene regulation implies that transcription factors gain access to genomic information via poorly understood processes involving activation and targeting of kinases, histone-modifying enzymes, and chromatin remodelers to chromatin. Here we report that progestin gene regulation in breast cancer cells requires a rapid and transient increase in poly-(ADP)-ribose (PAR), accompanied by a dramatic decrease of cellular NAD that could have broad implications in cell physiology. This rapid increase in nuclear PARylation is mediated by activation of PAR polymerase PARP-1 as a result of phosphorylation by cyclin-dependent kinase CDK2. Hormone-dependent phosphorylation of PARP-1 by CDK2, within the catalytic domain, enhances its enzymatic capabilities. Activated PARP-1 contributes to the displacement of histone H1 and is essential for regulation of the majority of hormone-responsive genes and for the effect of progestins on cell cycle progression. Both global chromatin immunoprecipitation (ChIP) coupled with deep sequencing (ChIP-seq) and gene expression analysis show a strong overlap between PARP-1 and CDK2. Thus, progestin gene regulation involves a novel signaling pathway that connects CDK2-dependent activation of PARP-1 with histone H1 displacement. Given the multiplicity of PARP targets, this new pathway could be used for the pharmacological management of breast cancer. PARP-1 activation mechanism by CDK2 in response of progestin in breast cancer cells
2014-01-08 | E-GEOD-53855 | biostudies-arrayexpress
Project description:Protein Kinase C alpha (PKC) is a critical mediator of cell signaling and cancer growth. We show that PKC inhibitors decrease proliferation in squamous cell carcinoma of the head and neck (SCCHN) cells and abrogate growth of SCCHN tumors in mouse xenografts. Analysis of gene expression arrays reveals that PKC regulates cell cycle genes required for DNA synthesis. In particular, PKC increases cyclin E protein expression, cyclinE/cdk2 complex formation, and transcription of cyclin E and E2F target genes. Consistent with this mechanism, expression of cyclin E rescues the block in DNA synthesis caused by PKC inhibition. In SCCHN tissue, PKC and cyclin E expression increase progressively from normal and dysplastic to malignant human head and neck tissue. Furthermore, PKCÂ expression correlates with poor prognosis in SCCHN. These results demonstrate that PKC regulates growth by stimulating DNA synthesis through cyclin E and E2F and identify PKC as a therapeutic target that is highly expressed in aggressive SCCHN. Experiment Overall Design: 9 samples composed of treated replicates at three time points
2009-03-28 | E-GEOD-10299 | biostudies-arrayexpress