Msn2/4 regulate expression of glycolytic enzymes and control transition from quiescence to growth

Abstract
Data availability
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Abstract

Nutrient availability and stresses impact a cell's decision to enter a growth state or a quiescent state. Acetyl-CoA stimulates cell growth under nutrient-limiting conditions, but how cells generate acetyl-CoA under starvation stress is less understood. Here, we show that general stress response factors, Msn2 and Msn4, function as master transcriptional regulators of yeast glycolysis via directly binding and activating genes encoding glycolytic enzymes. Yeast cells lacking Msn2 and Msn4 exhibit prevalent repression of glycolysis genes and a significant delay of acetyl-CoA accumulation and reentry into growth from quiescence. Thus Msn2/4 exhibit a dual role in activating carbohydrate metabolism genes and stress response genes. These results suggest a possible mechanism by which starvation-induced stress response factors may prime quiescent cells to reenter growth through glycolysis when nutrients are limited.

Data availability

The following data sets were generated

1. Kuang Z
2. Boeke JD
3. Ji H
(2017) DynaMO, a package identifying transcription factor binding sites in dynamical ChIPSeq/RNASeq datasets, identifies transcription factors driving yeast ultradian and mammalian circadian cycles
Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE72263).

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?token=ihypqcwenxkbluv&acc=GSE72263

The following previously published data sets were used

1. Kuang Z
2. Cai L
3. Zhang X
4. Ji H
5. Tu BP
6. Boeke JD
(2014) A high-resolution view of transcription and chromatin states across distinct metabolic states in budding yeast
Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE52339).

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE52339

Article and author information

Author details

Zheng Kuang

Institute for Systems Genetics, NYU Langone Medical Center, New York, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-5855-8371
Sudarshan Pinglay

Institute for Systems Genetics, NYU Langone Medical Center, New York, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-8781-1476
Hongkai Ji

Department of Biostatistics, Johns Hopkins University School of Public Health, Baltimore, United States

For correspondence
hji@jhu.edu

Competing interests
The authors declare that no competing interests exist.
Jef D Boeke

Institute for Systems Genetics, NYU Langone Medical Center, New York, United States

For correspondence
jef.boeke@nyumc.org

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-5322-4946

Funding

National Institutes of Health (U54GM103520)

Zheng Kuang
Jef D Boeke

National Institutes of Health (R01HG006841)

Zheng Kuang
Hongkai Ji

National Institutes of Health (R01HG006282)

Zheng Kuang
Hongkai Ji

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.