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Xbp1 directs global repression of budding yeast transcription during the transition to quiescence and is important for the longevity and reversibility of the quiescent state.

Miles S, Li L, Davison J, Breeden LL - PLoS Genet. (2013)

Bottom Line: Xbp1 is induced as glucose is depleted and it is among the most abundant transcripts in quiescent cells.The XBP1 transcript also undergoes metabolic oscillations under glucose limitation and we identified many additional transcripts that oscillate out of phase with XBP1 and have Xbp1 binding sites in their promoters.Further global analysis revealed that Xbp1 represses 15% of all yeast genes as they enter the quiescent state and over 500 of these transcripts contain Xbp1 binding sites in their promoters.

View Article: PubMed Central - PubMed

Affiliation: Basic Science Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.

ABSTRACT
Pure populations of quiescent yeast can be obtained from stationary phase cultures that have ceased proliferation after exhausting glucose and other carbon sources from their environment. They are uniformly arrested in the G1 phase of the cell cycle, and display very high thermo-tolerance and longevity. We find that G1 arrest is initiated before all the glucose has been scavenged from the media. Maintaining G1 arrest requires transcriptional repression of the G1 cyclin, CLN3, by Xbp1. Xbp1 is induced as glucose is depleted and it is among the most abundant transcripts in quiescent cells. Xbp1 binds and represses CLN3 transcription and in the absence of Xbp1, or with extra copies of CLN3, cells undergo ectopic divisions and produce very small cells. The Rad53-mediated replication stress checkpoint reinforces the arrest and becomes essential when Cln3 is overproduced. The XBP1 transcript also undergoes metabolic oscillations under glucose limitation and we identified many additional transcripts that oscillate out of phase with XBP1 and have Xbp1 binding sites in their promoters. Further global analysis revealed that Xbp1 represses 15% of all yeast genes as they enter the quiescent state and over 500 of these transcripts contain Xbp1 binding sites in their promoters. Xbp1-repressed transcripts are highly enriched for genes involved in the regulation of cell growth, cell division and metabolism. Failure to repress some or all of these targets leads xbp1 cells to enter a permanent arrest or senescence with a shortened lifespan.

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Related in: MedlinePlus

Xbp1 is important for maintaining a reversible quiescent state.(A) Percent budding as a function of time as purified Q cells are returned to fresh YEPD media and re-enter the cell cycle. (B) Long term viability and (C) colony formation of purified Q cells over 8 weeks of incubation in water. (D) Samples were taken from BY6500 wild type (WT) and xbp1 Q cells and 150 minutes after those Q cells were re-fed. Differential image contrast (DIC) and calcofluor-stained bud scars show the budded and unbudded populations. Relevant genotypes indicated (BY6500 wild type, BY6602 xbp1, BY6873 cln3, BY7131 cln3xbp1.).
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pgen-1003854-g004: Xbp1 is important for maintaining a reversible quiescent state.(A) Percent budding as a function of time as purified Q cells are returned to fresh YEPD media and re-enter the cell cycle. (B) Long term viability and (C) colony formation of purified Q cells over 8 weeks of incubation in water. (D) Samples were taken from BY6500 wild type (WT) and xbp1 Q cells and 150 minutes after those Q cells were re-fed. Differential image contrast (DIC) and calcofluor-stained bud scars show the budded and unbudded populations. Relevant genotypes indicated (BY6500 wild type, BY6602 xbp1, BY6873 cln3, BY7131 cln3xbp1.).

Mentions: The high level of induction of XBP1 suggests that it may be a major regulator during post-diauxic growth and in Q cells. Two other key properties of Q cells are their ability to rapidly reverse their arrest upon re-feeding, and their longevity during prolonged intervals of arrest. Xbp1 Q cells are defective in both of these processes. Figure 4A shows the recovery cycle of wild type and xbp1 Q cells upon re-feeding. Wild type Q cells have a 90 minute delay, followed by a highly synchronous cell cycle as monitored by budding. xbp1 Q cells initiate budding 30 minutes later and only about half the cells participate. The very small xbp1 Q cells show no indication of budding at the 150 minute time point (Figure 4D.) These small cells initiate budding two hours after wild type Q cells begin to bud.


Xbp1 directs global repression of budding yeast transcription during the transition to quiescence and is important for the longevity and reversibility of the quiescent state.

Miles S, Li L, Davison J, Breeden LL - PLoS Genet. (2013)

Xbp1 is important for maintaining a reversible quiescent state.(A) Percent budding as a function of time as purified Q cells are returned to fresh YEPD media and re-enter the cell cycle. (B) Long term viability and (C) colony formation of purified Q cells over 8 weeks of incubation in water. (D) Samples were taken from BY6500 wild type (WT) and xbp1 Q cells and 150 minutes after those Q cells were re-fed. Differential image contrast (DIC) and calcofluor-stained bud scars show the budded and unbudded populations. Relevant genotypes indicated (BY6500 wild type, BY6602 xbp1, BY6873 cln3, BY7131 cln3xbp1.).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3814307&req=5

pgen-1003854-g004: Xbp1 is important for maintaining a reversible quiescent state.(A) Percent budding as a function of time as purified Q cells are returned to fresh YEPD media and re-enter the cell cycle. (B) Long term viability and (C) colony formation of purified Q cells over 8 weeks of incubation in water. (D) Samples were taken from BY6500 wild type (WT) and xbp1 Q cells and 150 minutes after those Q cells were re-fed. Differential image contrast (DIC) and calcofluor-stained bud scars show the budded and unbudded populations. Relevant genotypes indicated (BY6500 wild type, BY6602 xbp1, BY6873 cln3, BY7131 cln3xbp1.).
Mentions: The high level of induction of XBP1 suggests that it may be a major regulator during post-diauxic growth and in Q cells. Two other key properties of Q cells are their ability to rapidly reverse their arrest upon re-feeding, and their longevity during prolonged intervals of arrest. Xbp1 Q cells are defective in both of these processes. Figure 4A shows the recovery cycle of wild type and xbp1 Q cells upon re-feeding. Wild type Q cells have a 90 minute delay, followed by a highly synchronous cell cycle as monitored by budding. xbp1 Q cells initiate budding 30 minutes later and only about half the cells participate. The very small xbp1 Q cells show no indication of budding at the 150 minute time point (Figure 4D.) These small cells initiate budding two hours after wild type Q cells begin to bud.

Bottom Line: Xbp1 is induced as glucose is depleted and it is among the most abundant transcripts in quiescent cells.The XBP1 transcript also undergoes metabolic oscillations under glucose limitation and we identified many additional transcripts that oscillate out of phase with XBP1 and have Xbp1 binding sites in their promoters.Further global analysis revealed that Xbp1 represses 15% of all yeast genes as they enter the quiescent state and over 500 of these transcripts contain Xbp1 binding sites in their promoters.

View Article: PubMed Central - PubMed

Affiliation: Basic Science Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.

ABSTRACT
Pure populations of quiescent yeast can be obtained from stationary phase cultures that have ceased proliferation after exhausting glucose and other carbon sources from their environment. They are uniformly arrested in the G1 phase of the cell cycle, and display very high thermo-tolerance and longevity. We find that G1 arrest is initiated before all the glucose has been scavenged from the media. Maintaining G1 arrest requires transcriptional repression of the G1 cyclin, CLN3, by Xbp1. Xbp1 is induced as glucose is depleted and it is among the most abundant transcripts in quiescent cells. Xbp1 binds and represses CLN3 transcription and in the absence of Xbp1, or with extra copies of CLN3, cells undergo ectopic divisions and produce very small cells. The Rad53-mediated replication stress checkpoint reinforces the arrest and becomes essential when Cln3 is overproduced. The XBP1 transcript also undergoes metabolic oscillations under glucose limitation and we identified many additional transcripts that oscillate out of phase with XBP1 and have Xbp1 binding sites in their promoters. Further global analysis revealed that Xbp1 represses 15% of all yeast genes as they enter the quiescent state and over 500 of these transcripts contain Xbp1 binding sites in their promoters. Xbp1-repressed transcripts are highly enriched for genes involved in the regulation of cell growth, cell division and metabolism. Failure to repress some or all of these targets leads xbp1 cells to enter a permanent arrest or senescence with a shortened lifespan.

Show MeSH
Related in: MedlinePlus