A novel allele of <i>SIR2</i> reveals a heritable intermediate state of gene silencing

Farris, Delaney; Saxton, Daniel S; Rine, Jasper

doi:10.1093/genetics/iyab041

Cited by 3 publications

(1 citation statement)

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“… 2005 ). Epigenetic silencing of the HMR / HML loci is a complex mechanism that requires the recruitment of the Sir complex and the presence of cis -acting silencers to assure that only the MAT locus is functionally active (Farris, Saxton and Rine 2021 ). The MAT locus contains one of two idiomorphs that comprises three regions Z, Y and X.…”

Section: Mating-type Loci and Genetic Switchingmentioning

confidence: 99%

Insights on life cycle and cell identity regulatory circuits for unlocking genetic improvement in Zygosaccharomyces and Kluyveromyces yeasts

Solieri

Cassanelli

Huff

et al. 2021

FEMS Yeast Research

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Evolution has provided a vast diversity of yeasts that play fundamental roles in nature and society. This diversity is not limited to genotypically homogenous species with natural interspecies hybrids and allodiploids that blur species boundaries frequently isolated. Thus, life-cycle and the nature of breeding systems have profound effects on genome variation, shaping heterozygosity, genotype diversity and ploidy level. The apparent enrichment of hybrids in industry-related environments suggests that hybridisation provides an adaptive route against stressors and creates interest in developing new hybrids for biotechnological uses. For example, in the Saccharomyces genus where regulatory circuits controlling cell-identity, mating competence and meiosis commitment have been extensively studied, this body of knowledge is being used to combine interesting traits into synthetic F1 hybrids, to by-pass F1 hybrid sterility, and to dissect complex phenotypes by bulk segregant analysis. Although there is less known about these aspects in other industrially-promising yeasts, advances in whole genome sequencing and analysis are changing this and new insights are being gained, especially in the food-associated genera Zygosaccharomyces and Kluyveromyces. We discuss this new knowledge and highlight how deciphering cell identity circuits in these lineages will contribute significantly to identify the genetic determinants underpinning complex phenotypes and open new avenues for breeding programmes.

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Section: Mating-type Loci and Genetic Switchingmentioning

confidence: 99%

Insights on life cycle and cell identity regulatory circuits for unlocking genetic improvement in Zygosaccharomyces and Kluyveromyces yeasts

Solieri

Cassanelli

Huff

et al. 2021

FEMS Yeast Research

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Novel interactions within the silent information regulator heterochromatin complex potentiate inter-subunit communication and gene repression

Kotz,

Martz,

Nelson

et al. 2024

Preprint

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Organisms with smaller genomes often perform multiple functions using one multi-subunit protein complex. TheS. cerevisiaeSilent Information Regulator complex (SIRc) carries out all of the core functions of heterochromatin. SIR complexes first drive the initiation and spreading of histone deacetylation in an iterative manner. Subsequently, the same complexes are incorporated stably with nucleosomes, driving compaction and repression of the underlying chromatin domain. These two distinct functions of SIRc have each been characterized in much detail, but the mechanism by which the dynamic spreading state switches to stable compaction is not well-understood. This incomplete knowledge of intra- complex communication is partly due to a lack of structural information of the complex as a whole; only structures of fragments have been determined to date. Using cross-linking mass spectrometry in solution, we identified a novel inter-subunit interaction that physically connects the two states of SIRc. The Sir2 deacetylase makes direct interactions with the scaffolding subunit Sir4 through its coiled-coil domain, which also interacts with the Sir3 compaction/repression subunit. Within the hub of interactions are conserved residues in Sir2 that can sense deacetylation state, as well as amino acids that likely diverged and co-evolved to interact with Sir4, promoting species-specific functions. Mutation of this interaction hub disrupts heterochromatic repression, potentially by disrupting a conserved mechanism that communicates completion of deacetylation to switch to compaction. Our work highlights how a single multi-functional chromatin regulatory complex can stage a step-wise mechanism that requires a major transition in activities to achieve epigenetic gene repression.

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Transcriptional silencing in Saccharomyces cerevisiae: known unknowns

Dhillon,

Kamakaka

2024

Epigenetics & Chromatin

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Transcriptional silencing in Saccharomyces cerevisiae is a persistent and highly stable form of gene repression. It involves DNA silencers and repressor proteins that bind nucleosomes. The silenced state is influenced by numerous factors including the concentration of repressors, nature of activators, architecture of regulatory elements, modifying enzymes and the dynamics of chromatin.Silencers function to increase the residence time of repressor Sir proteins at silenced domains while clustering of silenced domains enables increased concentrations of repressors and helps facilitate long-range interactions. The presence of an accessible NDR at the regulatory regions of silenced genes, the cycling of chromatin configurations at regulatory sites, the mobility of Sir proteins, and the non-uniform distribution of the Sir proteins across the silenced domain, all result in silenced chromatin that only stably silences weak promoters and enhancers via changes in transcription burst duration and frequency.These data collectively suggest that silencing is probabilistic and the robustness of silencing is achieved through sub-optimization of many different nodes of action such that a stable expression state is generated and maintained even though individual constituents are in constant flux.

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A novel allele of SIR2 reveals a heritable intermediate state of gene silencing

Cited by 3 publications

References 47 publications

Insights on life cycle and cell identity regulatory circuits for unlocking genetic improvement in Zygosaccharomyces and Kluyveromyces yeasts

Insights on life cycle and cell identity regulatory circuits for unlocking genetic improvement in Zygosaccharomyces and Kluyveromyces yeasts

Novel interactions within the silent information regulator heterochromatin complex potentiate inter-subunit communication and gene repression

Transcriptional silencing in Saccharomyces cerevisiae: known unknowns

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