Limits to transcriptional silencing in <i>Saccharomyces cerevisiae</i>

Fouet, Marc; Rine, Jasper

doi:10.1093/genetics/iyac180

Cited by 4 publications

(6 citation statements)

References 49 publications

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“…An example for such constitutive silencing would be the HML and HMR mating type loci in S. cerevisiae (26). Under the state of constitutive repression, various defects in cis-acting silencing factors or in the progression of replication forks can lead to transient de-repression or a bi-fold state, depending on the nature of the mutation (12,27,28). A second mode of epigenetic silencing would be a normal bi-fold Active/Silent state.…”

Section: Discussionmentioning

confidence: 99%

Analyses of POL30 (PCNA) reveal positional effects in transient repression or bi-fold active/silent state at the sub-telomeres of S. cerevisiae

Sauty

Yankulov

2023

Preprint

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Background Classical studies on position effect variegation in Drosophila have demonstrated the existence of bi-modal Active/Silent state of the genes juxtaposed to heterochromatin. Later studies with irreversible methods for the detection of gene repression have revealed a similar phenomenon at the telomeres of Saccharomyces cerevisiae and other species. In this study, we used dual reporter constructs and a combination of reversible and non-reversible methods to present evidence for the existence of different states of gene repression at the sub-telomeres of S. cerevisiae. Results We show position dependent transient repression or bimodal expression of reporter genes at the VIIL sub-telomere. We also show that mutations in the replicative clamp POL30 (PCNA) or the destruction of the histone chaperone CAF1 or the RRM3 helicase lead to transient de-repression, while the destruction of the histone chaperone ASF1 causes a shift from transient de-repression to a bi-modal state of repression. We analyze the physical interaction of CAF1 and RRM3 with PCNA and discuss the implications of these findings for our understanding of the stability and transmission of the epigenetic state of the genes. Conclusions There are distinct modes of gene silencing, bi-modal and transient, at the sub-telomeres of S. cerevisiae. We characterise the roles of CAF1, RRM3 and ASF1 in these modes of gene repression. We suggest that the interpretations of past and future studies should consider the existence of the dissimilar states of gene silencing.

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Section: Discussionmentioning

confidence: 99%

Analyses of POL30 (PCNA) reveal positional effects in transient repression or bi-fold active/silent state at the sub-telomeres of S. cerevisiae

Sauty

Yankulov

2023

Preprint

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“…An example for such constitutive silencing would be the HML and HMR mating type loci in S. cerevisiae [ 26 ] . Under the state of constitutive repression, various defects in cis-acting silencing factors or in the progression of replication forks can lead to transient de-repression or a bi-modal state, depending on the nature of the mutation [ 12 , 27 , 28 ] . A second mode of epigenetic silencing would be a normal bi-modal Active/Silent state.…”

Section: Discussionmentioning

confidence: 99%

Analyses of POL30 (PCNA) reveal positional effects in transient repression or bi-modal active/silent state at the sub-telomeres of S. cerevisiae

Sauty,

Yankulov

2023

Epigenetics & Chromatin

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Background Classical studies on position effect variegation in Drosophila have demonstrated the existence of bi-modal Active/Silent state of the genes juxtaposed to heterochromatin. Later studies with irreversible methods for the detection of gene repression have revealed a similar phenomenon at the telomeres of Saccharomyces cerevisiae and other species. In this study, we used dual reporter constructs and a combination of reversible and non-reversible methods to present evidence for the different roles of PCNA and histone chaperones in the stability and the propagation of repressed states at the sub-telomeres of S. cerevisiae. Results We show position dependent transient repression or bi-modal expression of reporter genes at the VIIL sub-telomere. We also show that mutations in the replicative clamp POL30 (PCNA) or the deletion of the histone chaperone CAF1 or the RRM3 helicase lead to transient de-repression, while the deletion of the histone chaperone ASF1 causes a shift from transient de-repression to a bi-modal state of repression. We analyze the physical interaction of CAF1 and RRM3 with PCNA and discuss the implications of these findings for our understanding of the stability and transmission of the epigenetic state of the genes. Conclusions There are distinct modes of gene silencing, bi-modal and transient, at the sub-telomeres of S. cerevisiae. We characterise the roles of CAF1, RRM3 and ASF1 in these modes of gene repression. We suggest that the interpretations of past and future studies should consider the existence of the dissimilar states of gene silencing.

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“…This experiment was carried out as described in refs. 49 and 87 . The apparent silencing-loss rate was calculated as previously described ( 49 , 87 ) ( SI Appendix , Supplementary Methods ).…”

Section: Methodsmentioning

confidence: 99%

Context-dependent function of the transcriptional regulator Rap1 in gene silencing and activation in Saccharomyces cerevisiae

Bondra,

Rine

2023

Proc. Natl. Acad. Sci. U.S.A.

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In Saccharomyces cerevisiae, heterochromatin is formed through interactions between site-specific DNA-binding factors, including the transcriptional activator Repressor Activator Protein (Rap1), and Sir proteins. Despite an understanding of the establishment and maintenance of Sir-silenced chromatin, the mechanism of gene silencing by Sir proteins has remained a mystery. Utilizing high-resolution chromatin immunoprecipitation, we found that Rap1, the native activator of the bidirectional HML α promoter, bound its recognition sequence in silenced chromatin, and its binding was enhanced by the presence of Sir proteins. In contrast to prior results, various components of transcription machinery were not able to access HML α in the silenced state. These findings disproved the long-standing model of indiscriminate steric occlusion by Sir proteins and led to investigation of the role of the transcriptional activator Rap1 in Sir-silenced chromatin. Using a highly sensitive assay that monitors loss-of-silencing events, we identified a role for promoter-bound Rap1 in the maintenance of silent chromatin through interactions with the Sir complex. We also found that promoter-bound Rap1 activated HML α when in an expressed state, and aided in the transition from transcription initiation to elongation. Highlighting the importance of epigenetic context in transcription factor function, these results point toward a model in which the duality of Rap1 function was mediated by local chromatin environment rather than binding-site availability.

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Limits to transcriptional silencing in Saccharomyces cerevisiae

Cited by 4 publications

References 49 publications

Analyses of POL30 (PCNA) reveal positional effects in transient repression or bi-fold active/silent state at the sub-telomeres of S. cerevisiae

Analyses of POL30 (PCNA) reveal positional effects in transient repression or bi-fold active/silent state at the sub-telomeres of S. cerevisiae

Analyses of POL30 (PCNA) reveal positional effects in transient repression or bi-modal active/silent state at the sub-telomeres of S. cerevisiae

Context-dependent function of the transcriptional regulator Rap1 in gene silencing and activation in Saccharomyces cerevisiae

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