Allantoin Degradation bySaccharomyces Cerevisiae-a Model System for Gene Regulation and Metabolic Integration

Author(s):  
Terrance G. Cooper
mBio ◽  
2013 ◽  
Vol 4 (6) ◽  
Author(s):  
Jörg Schumacher ◽  
Volker Behrends ◽  
Zhensheng Pan ◽  
Dan R. Brown ◽  
Franziska Heydenreich ◽  
...  

ABSTRACTNitrogen regulation inEscherichia coliis a model system for gene regulation in bacteria. Growth on glutamine as a sole nitrogen source is assumed to be nitrogen limiting, inferred from slow growth and strong NtrB/NtrC-dependent gene activation. However, we show that under these conditions, the intracellular glutamine concentration is not limiting but 5.6-fold higher than in ammonium-replete conditions; in addition, α-ketoglutarate concentrations are elevated. We address this glutamine paradox from a systems perspective. We show that the dominant role of NtrC is to regulateglnAtranscription and its own expression, indicating that the glutamine paradox is not due to NtrC-independent gene regulation. The absolute intracellular NtrC and GS concentrations reveal molecular control parameters, where NtrC-specific activities were highest in nitrogen-starved cells, while under glutamine growth, NtrC showed intermediate specific activity. We propose anin vivomodel in which α-ketoglutarate can derepress nitrogen regulation despite nitrogen sufficiency.IMPORTANCENitrogen is the most important nutrient for cell growth after carbon, and its metabolism is coordinated at the metabolic, transcriptional, and protein levels. We show that growth on glutamine as a sole nitrogen source, commonly assumed to be nitrogen limiting and used as such as a model system for nitrogen limitation, is in fact nitrogen replete. Our integrative quantitative analysis of key molecules involved in nitrogen assimilation and regulation reveal that glutamine is not necessarily the dominant molecule signaling nitrogen sufficiency and that α-ketoglutarate may play a more important role in signaling nitrogen status. NtrB/NtrC integrates α-ketoglutarate and glutamine signaling—sensed by the UTase (glnD) and PII (glnB), respectively—and regulates the nitrogen response through self-regulated expression and phosphorylation-dependent activation of the nitrogen (ntr) regulon. Our findings support α-ketoglutarate acting as a global regulatory metabolite.


1989 ◽  
Vol 27 ◽  
pp. 3
Author(s):  
M. Montagu van ◽  
D. Valvekens ◽  
M. van Lijsebettens ◽  
G. Gheysen ◽  
J. Okamuro ◽  
...  
Keyword(s):  

Endocrinology ◽  
2012 ◽  
Vol 153 (11) ◽  
pp. 5309-5324 ◽  
Author(s):  
Saurabh S. Kulkarni ◽  
Daniel R. Buchholz

Abstract Hormones play critical roles in vertebrate development, and frog metamorphosis has been an excellent model system to study the developmental roles of thyroid hormone (TH) and glucocorticoids. Whereas TH regulates the initiation and rate of metamorphosis, the actions of corticosterone (CORT; the main glucocorticoid in frogs) are more complex. In the absence of TH during premetamorphosis, CORT inhibits development, but in the presence of TH during metamorphosis, CORT synergizes with TH to accelerate development. Synergy at the level of gene expression is known for three genes in frogs, but the nature and extent of TH and CORT cross talk is otherwise unknown. Therefore, to examine TH and CORT interactions, we performed microarray analysis on tails from Xenopus tropicalis tadpoles treated with CORT, TH, CORT+TH, or vehicle for 18 h. The expression of 5432 genes was significantly altered in response to either or both hormones. Using Venn diagrams and cluster analysis, we identified 16 main patterns of gene regulation due to up- or down-regulation by TH and/or CORT. Many genes were affected by only one of the hormones, and a large proportion of regulated genes (22%) required both hormones. We also identified patterns of additive or synergistic, inhibitory, subtractive, and annihilatory regulation. A total of 928 genes (17%) were regulated by novel interactions between the two hormones. These data expand our understanding of the hormonal cross talk underlying the gene regulation cascade directing tail resorption and suggest the possibility that CORT affects not only the timing but also the nature of TH-dependent tissue transformation.


2000 ◽  
Vol 28 (4) ◽  
pp. 376-379 ◽  
Author(s):  
I. Whitehouse ◽  
A. Flaus ◽  
K. Havas ◽  
T. Owen-Hughes

Gene regulation involves the generation of a local chromatin topology that is conducive to transcription. Several classes of chromatin remodelling activity have been shown to play a role in this process. ATP-dependent chromatin-remodelling activities use energy derived from the hydrolysis of ATP to alter the structure of chromatin, making it more accessible for transcription factor binding. The yeast SWI-SWF complex is the founding member of this family of ATP-dependent chromatin-remodelling activities. We have developed a model system to study the ability of the SWI-SWF complex to alter chromatin structure. Using this system, we find that SWI-SWF is able to alter the position of nucleosomes along the DNA. This is consistent with recent reports that other ATP-dependent chromatin-remodelling activities can alter the positions of nucleosomes along DNA. This suggests that nucleosome mobilization may be a general feature of the activity of ATP-dependent chromatin-remodelling activities. Some of the mechanisms by which nucleosomes may be moved along DNA are discussed.


1987 ◽  
Vol 5 (5) ◽  
pp. 469-477 ◽  
Author(s):  
V. Deretic ◽  
J. F. Gill ◽  
A. M. Chakrabarty

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