TY - JOUR
T1 - Existence, transition, and propagation of intermediate silencing states in ribosomal DNA
AU - Zou, Fan
AU - Du, Manyu
AU - Chen, Hengye
AU - Baia, Lu
N1 - Funding Information:
We are grateful to all members of the Bai lab for insightful comments on the manuscript. This work is supported by the National Institutes of Health (R01 GM118682).
Publisher Copyright:
© 2019 American Society for Microbiology. All Rights Reserved.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - The MET3 promoter (MET3pr) inserted into the silenced chromosome in budding yeast can overcome Sir2-dependent silencing upon induction and activate transcription in every single cell among a population. Despite the fact that MET3pr is turned on in all the cells, its activity still shows very high cell-to-cell variability. To understand the nature of such “gene expression noise,” we followed the dynamics of the MET3pr-GFP expression inserted into ribosomal DNA (rDNA) using time-lapse microscopy. We found that the noisy “on” state is comprised of multiple substable states with discrete expression levels. These intermediate states stochastically transition between each other, with “up” transitions among different activated states occurring exclusively near the mitotic exit and “down” transitions occurring throughout the rest of the cell cycle. Such cell cycle dependence likely reflects the dynamic activity of the rDNA-specific RENT complex, as MET3pr-GFP expression in a telomeric locus does not have the same cell cycle dependence. The MET3pr-GFP expression in rDNA is highly correlated in mother and daughter cells after cell division, indicating that the silenced state in the mother cell is inherited in daughter cells. These states are disrupted by a brief repression and reset upon a second activation. Potential mechanisms behind these observations are further discussed.
AB - The MET3 promoter (MET3pr) inserted into the silenced chromosome in budding yeast can overcome Sir2-dependent silencing upon induction and activate transcription in every single cell among a population. Despite the fact that MET3pr is turned on in all the cells, its activity still shows very high cell-to-cell variability. To understand the nature of such “gene expression noise,” we followed the dynamics of the MET3pr-GFP expression inserted into ribosomal DNA (rDNA) using time-lapse microscopy. We found that the noisy “on” state is comprised of multiple substable states with discrete expression levels. These intermediate states stochastically transition between each other, with “up” transitions among different activated states occurring exclusively near the mitotic exit and “down” transitions occurring throughout the rest of the cell cycle. Such cell cycle dependence likely reflects the dynamic activity of the rDNA-specific RENT complex, as MET3pr-GFP expression in a telomeric locus does not have the same cell cycle dependence. The MET3pr-GFP expression in rDNA is highly correlated in mother and daughter cells after cell division, indicating that the silenced state in the mother cell is inherited in daughter cells. These states are disrupted by a brief repression and reset upon a second activation. Potential mechanisms behind these observations are further discussed.
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U2 - 10.1128/MCB.00146-19
DO - 10.1128/MCB.00146-19
M3 - Article
C2 - 31527077
AN - SCOPUS:85074964660
SN - 0270-7306
VL - 39
JO - Molecular and cellular biology
JF - Molecular and cellular biology
IS - 23
M1 - e00146-19
ER -