Gcn4 negatively regulates expression of genes subjected to nitrogen catabolite repression

Sosa, E. Rodolfo; Aranda, Cristina; Riego, Lina; Valenzuela, Lourdes; DeLuna, Alexander; Cantú, J. M.; González, Alicia

doi:10.1016/j.bbrc.2003.09.144

Cited by 17 publications

(16 citation statements)

References 18 publications

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“…In addition, Gcn4 was identified in this study as a nitrogen catabolite repression (NCR) target, with its expression decreased under nitrogen-abundant conditions. A putative cross talk between CPC and NCR in S. cerevisiae remains ambiguous, although there are indications for a role for Gcn4 in NCR by repressing Gln3 and for the repression of Gcn4 translation under nitrogen starvation conditions (25,67). This is in clear contradiction to our finding that cpc1 is upregulated by glutamine addition and in the areA mutant (Fig.…”

Section: Discussioncontrasting

confidence: 99%

Cross-Species Hybridization with Fusarium verticillioides Microarrays Reveals New Insights into Fusarium fujikuroi Nitrogen Regulation and the Role of AreA and NMR

et al. 2008

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In filamentous fungi, the GATA-type transcription factor AreA plays a major role in the transcriptional activation of genes needed to utilize poor nitrogen sources. In Fusarium fujikuroi, AreA also controls genes involved in the biosynthesis of gibberellins, a family of diterpenoid plant hormones. To identify more genes responding to nitrogen limitation or sufficiency in an AreA-dependent or -independent manner, we examined changes in gene expression of F. fujikuroi wild-type and ⌬areA strains by use of a Fusarium verticillioides microarray representing ϳ9,300 genes. Analysis of the array data revealed sets of genes significantly down-and upregulated in the areA mutant under both N starvation and N-sufficient conditions. Among the downregulated genes are those involved in nitrogen metabolism, e.g., those encoding glutamine synthetase and nitrogen permeases, but also those involved in secondary metabolism. Besides AreA-dependent genes, we found an even larger set of genes responding to N starvation and N-sufficient conditions in an AreA-independent manner. To study the impact of NMR on AreA activity, we examined the expression of several AreA target genes in the wild type and in areA and nmr deletion and overexpression mutants. We show that NMR interacts with AreA as expected but affects gene expression only in early growth stages. This is the first report on genome-wide expression studies examining the influence of AreA on nitrogen-responsive gene expression in a genome-wide manner in filamentous fungi.

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Section: Discussioncontrasting

confidence: 99%

Cross-Species Hybridization with Fusarium verticillioides Microarrays Reveals New Insights into Fusarium fujikuroi Nitrogen Regulation and the Role of AreA and NMR

et al. 2008

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“…Our data reveal that the expression of GCN4, encoding the principal transcription factor of GAAC, depends on the nitrogen source supplied and is subject to NCR. On the other hand, previous work has highlighted a contribution of Gcn4 to NCR (118). Together these data suggest a possible general crossregulation between the two major transcriptional controls of nitrogenous anabolism and catabolism in yeast, in which NCR (most active on good nitrogen sources) would down-regulate GAAC, which in turn would up-regulate NCR.…”

Section: Discussionmentioning

confidence: 67%

“…Some of these regulatory genes encode proteins known to be directly involved in the regulation of nitrogen metabolism genes. For instance, we mention above a role of NCR in the transcriptional control of the GCN4 gene, while this gene appears to be required for optimal NCR (118). We have also identified two probable NCR target genes encoding potentially interesting regulatory factors, including one (LEE1/YPL054W) which may be involved in controlling mRNA stability.…”

Section: Discussionmentioning

confidence: 84%

“…Furthermore, Gln3 has been associated with the GCN4 locus in ChIP-chip experiments (7), and our data of RT-qPCR experiments showed that GCN4 expression is significantly derepressed in a mutant strain defective in NCR (see Table S4 in the supplemental material). While these observations indicate that the transcription of GCN4 is subject to NCR, two other studies have highlighted a positive contribution of Gcn4 in NCR (118,128), thus suggesting some cross-regulation between NCR and GAAC (see Discussion). Yet another transcription factor gene classified as an NCR target is UGA3, in keeping with a recent report (65).…”

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confidence: 78%

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Effect of 21 Different Nitrogen Sources on Global Gene Expression in the YeastSaccharomyces cerevisiae

Godard

Urrestarazu

Vissers

et al. 2007

Molecular and Cellular Biology

217

270

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We compared the transcriptomes of Saccharomyces cerevisiae cells growing under steady-state conditions on 21 unique sources of nitrogen. We found 506 genes differentially regulated by nitrogen and estimated the activation degrees of all identified nitrogen-responding transcriptional controls according to the nitrogen source. One main group of nitrogenous compounds supports fast growth and a highly active nitrogen catabolite repression (NCR) control. Catabolism of these compounds typically yields carbon derivatives directly assimilable by a cell's metabolism. Another group of nitrogen compounds supports slower growth, is associated with excretion by cells of nonmetabolizable carbon compounds such as fusel oils, and is characterized by activation of the general control of amino acid biosynthesis (GAAC). Furthermore, NCR and GAAC appear interlinked, since expression of the GCN4 gene encoding the transcription factor that mediates GAAC is subject to NCR. We also observed that several transcriptional-regulation systems are active under a wider range of nitrogen supply conditions than anticipated. Other transcriptional-regulation systems acting on genes not involved in nitrogen metabolism, e.g., the pleiotropic-drug resistance and the unfolded-protein response systems, also respond to nitrogen. We have completed the lists of target genes of several nitrogen-sensitive regulons and have used sequence comparison tools to propose functions for about 20 orphan genes. Similar studies conducted for other nutrients should provide a more complete view of alternative metabolic pathways in yeast and contribute to the attribution of functions to many other orphan genes.

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“…Gcn4 is the transcription factor responsible for stimulating expression of .500 genes, including those of amino acid biosynthesis (Garcia-Barrio et al 2000;Krishnamurthy et al 2001;Hinnebusch 2005;Natarajan et al 2001Staschke et al 2010. Gcn4 additionally participates in combination with Gln3 to coactivate transcription of a small number of specific NCR-sensitive genes whose promoters contain Gcn4 binding sites (Mitchell and Magasanik 1984;Natarajan et al 2001;Valenzuela et al 2001, data set URL is no longer active; Riego et al 2002;Sosa et al 2003;Staschke et al 2010;Hernández et al 2011). On the other hand, when charged tRNAs are in excess, Gcn2-mediated regulatory outcomes are reversed.…”

Section: Candidates To Join Mtorc1 In Cumulative Gln3 Regulationmentioning

confidence: 99%

General Amino Acid Control and 14-3-3 Proteins Bmh1/2 Are Required for Nitrogen Catabolite Repression-Sensitive Regulation of Gln3 and Gat1 Localization

Tate¹,

Buford²,

Rai³

et al. 2017

Genetics

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Nitrogen catabolite repression (NCR), the ability of Saccharomyces cerevisiae to use good nitrogen sources in preference to poor ones, derives from nitrogen-responsive regulation of the GATA family transcription activators Gln3 and Gat1. In nitrogen-replete conditions, the GATA factors are cytoplasmic and NCR-sensitive transcription minimal. When only poor nitrogen sources are available, Gln3 is nuclear, dramatically increasing GATA factor-mediated transcription. This regulation was originally attributed to mechanistic Tor protein kinase complex 1 (mTorC1)-mediated control of Gln3. However, we recently showed that two regulatory systems act cumulatively to maintain cytoplasmic Gln3 sequestration, only one of which is mTorC1. Present experiments demonstrate that the other previously elusive component is uncharged transfer RNA-activated, Gcn2 protein kinase-mediated general amino acid control (GAAC). Gcn2 and Gcn4 are required for NCR-sensitive nuclear Gln3-Myc 13 localization, and from epistasis experiments Gcn2 appears to function upstream of Ure2. Bmh1/2 are also required for nuclear Gln3-Myc 13 localization and appear to function downstream of Ure2. Overall, Gln3 phosphorylation levels decrease upon loss of Gcn2, Gcn4, or Bmh1/2. Our results add a new dimension to nitrogenresponsive GATA-factor regulation and demonstrate the cumulative participation of the mTorC1 and GAAC pathways, which respond oppositely to nitrogen availability, in the nitrogen-responsive control of catabolic gene expression in yeast.

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Gcn4 negatively regulates expression of genes subjected to nitrogen catabolite repression

Cited by 17 publications

References 18 publications

Cross-Species Hybridization with Fusarium verticillioides Microarrays Reveals New Insights into Fusarium fujikuroi Nitrogen Regulation and the Role of AreA and NMR

Cross-Species Hybridization with Fusarium verticillioides Microarrays Reveals New Insights into Fusarium fujikuroi Nitrogen Regulation and the Role of AreA and NMR

Effect of 21 Different Nitrogen Sources on Global Gene Expression in the YeastSaccharomyces cerevisiae

General Amino Acid Control and 14-3-3 Proteins Bmh1/2 Are Required for Nitrogen Catabolite Repression-Sensitive Regulation of Gln3 and Gat1 Localization

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