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Review
. 2021 Mar 4:12:630506.
doi: 10.3389/fgene.2021.630506. eCollection 2021.

Variation, Variegation and Heritable Gene Repression in S. cerevisiae

Kholoud Shaban  1 , Safia Mahabub Sauty  1 , Krassimir Yankulov  1
Affiliations
Review

Variation, Variegation and Heritable Gene Repression in S. cerevisiae

Kholoud Shaban et al. Front Genet. .

Abstract

Phenotypic heterogeneity provides growth advantages for a population upon changes of the environment. In S. cerevisiae, such heterogeneity has been observed as "on/off" states in the expression of individual genes in individual cells. These variations can persist for a limited or extended number of mitotic divisions. Such traits are known to be mediated by heritable chromatin structures, by the mitotic transmission of transcription factors involved in gene regulatory circuits or by the cytoplasmic partition of prions or other unstructured proteins. The significance of such epigenetic diversity is obvious, however, we have limited insight into the mechanisms that generate it. In this review, we summarize the current knowledge of epigenetically maintained heterogeneity of gene expression and point out similarities and converging points between different mechanisms. We discuss how the sharing of limiting repression or activation factors can contribute to cell-to-cell variations in gene expression and to the coordination between short- and long- term epigenetic strategies. Finally, we discuss the implications of such variations and strategies in adaptation and aging.

Keywords: chromatin; diversity; gene regulatory circuits; gene repression; gene silencing; long non-coding RNA; phenotypic heterogeneity.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Models for meta-stable gene expression. The figure is available online as an animated PowerPoint® file to better present the sequence of events in the described processes. (A) A general model for meta-stability in eukaryotes: Position-Effect Variegation (PEV) at the peri-cenrtic heterochromatin of Drosophila. (B) Continuous and discontinuous spreading of histone deacetylation, chromatin boundaries and meta-stability at the telomeres of S. cerevisiae. (C) Epigenetic variations and meta-stability by recruitment into a nuclear heterochromatin domain.
FIGURE 2
FIGURE 2
Position-independent meta-stability at FLO1 and FLO11. The figure is available online as an animated PowerPoint® file to better present the sequence of events in the described processes. (A) FLO1. (B) FLO11.
FIGURE 3
FIGURE 3
DNA replication-coupled chromatin disassembly and reassembly. The figure is available online as an animated PowerPoint® file to better present the sequence of events in the described processes. (A) A model for DNA replication-coupled chromatin disassembly-reassembly and symmetric distribution of old H3/H4 tetramers. (B) Asymmetric distribution of old H3/H4 dimers in various mutants. (C) Loss of epigenetic marks as the fork pauses or slows down.
FIGURE 4
FIGURE 4
Gene regulatory circuits and bi-modal expression of GAL genes. The figure is available online as an animated PowerPoint® file to better present the sequence of events in the described processes.
FIGURE 5
FIGURE 5
Simulation of long-term and short-term epigenetic memory. The figure is available online as an animated PowerPoint® file to better present the sequence of events in the described processes. (A) Calculation of the proportion of cells (Y) with active (A) and repressed (R) state of a given gene in a population of cells. (B) A meta-stable locus with low frequency of epigenetic conversions. (C) Unstable bi-modal locus with high frequency of epigenetic conversions.
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