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Title: Bimodal expression of yeast GAL genes is controlled by a long non-coding RNA and a bifunctional galactokinase

Abstract

Bimodality in gene expression can generate phenotypic heterogeneity facilitating fitness and growth of isogenic cell populations in suboptimal environments. We investigated the mechanism by which, in conditions of limiting galactose, yeast cell populations activate GAL genes in a bimodal fashion with a cell fraction expressing GAL genes (ON), while the rest subpopulation is kept at the non-expressing (OFF) state. We show that a long non-coding RNA (GAL10-ncRNA) crossing the bidirectional GAL1-10 promoter, decreases the rate by which single cells commit transition to the ON state without affecting the rate of GAL transcription per se in ON cells. This is accomplished by repressing stochastic expression of the bifunctional Gal1p galactokinase, which besides its enzymatic activity acts as an essential inducer of the system under those conditions. We show that once single cells switch to the ON state, the GAL10-ncRNA effect is overridden by accumulating Gal1p levels sufficient to feedback positively on Gal4p, and not by the active transcription of GAL10 that occurs in opposite direction relative to that of GAL10-ncRNA. Conversely, GAL10-ncRNA does not influence transition of ON cells, where Gal4p is active, back to the OFF state. Our model suggests that the functional interplay between GAL10-ncRNA transcription, stochastic Gal1p expressionmore » and Gal1p positive feedback on Gal4p constitutes a novel molecular switch mechanism dictating the commitment of individual cells for either metabolic state. - Highlights: • Stochastic transcription of the Gal1p galactokinase creates bimodality in GAL expression. • GAL10-ncRNA controls GAL bimodality by repressing Gal1p. • GAL10-ncRNA repression is overridden by the inducing activity of Gal1p itself.« less

Authors:
;
Publication Date:
OSTI Identifier:
22696974
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 486; Journal Issue: 1; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; GENES; PLANT GROWTH; RNA; STOCHASTIC PROCESSES; TRANSCRIPTION; YEASTS

Citation Formats

Zacharioudakis, Ioannis, and Tzamarias, Dimitris. Bimodal expression of yeast GAL genes is controlled by a long non-coding RNA and a bifunctional galactokinase. United States: N. p., 2017. Web. doi:10.1016/J.BBRC.2017.02.127.
Zacharioudakis, Ioannis, & Tzamarias, Dimitris. Bimodal expression of yeast GAL genes is controlled by a long non-coding RNA and a bifunctional galactokinase. United States. https://doi.org/10.1016/J.BBRC.2017.02.127
Zacharioudakis, Ioannis, and Tzamarias, Dimitris. 2017. "Bimodal expression of yeast GAL genes is controlled by a long non-coding RNA and a bifunctional galactokinase". United States. https://doi.org/10.1016/J.BBRC.2017.02.127.
@article{osti_22696974,
title = {Bimodal expression of yeast GAL genes is controlled by a long non-coding RNA and a bifunctional galactokinase},
author = {Zacharioudakis, Ioannis and Tzamarias, Dimitris},
abstractNote = {Bimodality in gene expression can generate phenotypic heterogeneity facilitating fitness and growth of isogenic cell populations in suboptimal environments. We investigated the mechanism by which, in conditions of limiting galactose, yeast cell populations activate GAL genes in a bimodal fashion with a cell fraction expressing GAL genes (ON), while the rest subpopulation is kept at the non-expressing (OFF) state. We show that a long non-coding RNA (GAL10-ncRNA) crossing the bidirectional GAL1-10 promoter, decreases the rate by which single cells commit transition to the ON state without affecting the rate of GAL transcription per se in ON cells. This is accomplished by repressing stochastic expression of the bifunctional Gal1p galactokinase, which besides its enzymatic activity acts as an essential inducer of the system under those conditions. We show that once single cells switch to the ON state, the GAL10-ncRNA effect is overridden by accumulating Gal1p levels sufficient to feedback positively on Gal4p, and not by the active transcription of GAL10 that occurs in opposite direction relative to that of GAL10-ncRNA. Conversely, GAL10-ncRNA does not influence transition of ON cells, where Gal4p is active, back to the OFF state. Our model suggests that the functional interplay between GAL10-ncRNA transcription, stochastic Gal1p expression and Gal1p positive feedback on Gal4p constitutes a novel molecular switch mechanism dictating the commitment of individual cells for either metabolic state. - Highlights: • Stochastic transcription of the Gal1p galactokinase creates bimodality in GAL expression. • GAL10-ncRNA controls GAL bimodality by repressing Gal1p. • GAL10-ncRNA repression is overridden by the inducing activity of Gal1p itself.},
doi = {10.1016/J.BBRC.2017.02.127},
url = {https://www.osti.gov/biblio/22696974}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 1,
volume = 486,
place = {United States},
year = {Sat Apr 22 00:00:00 EDT 2017},
month = {Sat Apr 22 00:00:00 EDT 2017}
}