Telomere Structure Regulates the Heritability of Repressed Subtelomeric Chromatin in Saccharomyces cerevisiae

Abstract Telomeres, the protein-DNA structures present at the termini of linear chromosomes, are capable of conferring a reversible repression of Pol II- and Pol III-transcribed genes positioned in adjacent subtelomeric regions. This phenomenon, termed telomeric silencing, is likely to be the consequence of a more global telomere position effect at the level of chromatin structure. To understand the role of telomere structure in this position effect, we have developed an assay to distinguish between the heritability of transcriptionally repressed and derepressed states in yeast. We have previously demonstrated that an elongated telomeric tract leads to hyperrepression of telomere-adjacent genes. We show here that the predominant effect of elongated telomeres is to increase the inheritance of the repressed state in cis. Interestingly, the presence of elongated telomeres overcomes the partial requirement of yCAF-1 in silencing. We propose that the formation of a specific telomeric structure is necessary for the heritability of repressed subtelomeric chromatin.

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Telomeric and Sub-Telomeric Structure and Implications in Fungal Opportunistic Pathogens

Microorganisms ◽

10.3390/microorganisms9071405 ◽

2021 ◽

Vol 9 (7) ◽

pp. 1405

Author(s):

Raffaella Diotti ◽

Michelle Esposito ◽

Chang Hui Shen

Keyword(s):

Fungal Pathogens ◽

Functional Abilities ◽

Opportunistic Pathogens ◽

Telomeric Sequences ◽

Coding Regions ◽

Telomeric Structure ◽

Linear Chromosomes ◽

Dna Ends ◽

Telomere Structure

Telomeres are long non-coding regions found at the ends of eukaryotic linear chromosomes. Although they have traditionally been associated with the protection of linear DNA ends to avoid gene losses during each round of DNA replication, recent studies have demonstrated that the role of these sequences and their adjacent regions go beyond just protecting chromosomal ends. Regions nearby to telomeric sequences have now been identified as having increased variability in the form of duplications and rearrangements that result in new functional abilities and biodiversity. Furthermore, unique fungal telomeric and chromatin structures have now extended clinical capabilities and understanding of pathogenicity levels. In this review, telomere structure, as well as functional implications, will be examined in opportunistic fungal pathogens, including Aspergillus fumigatus, Candida albicans, Candida glabrata, and Pneumocystis jirovecii.

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Modifiers of Terminal Deficiency-Associated Position Effect Variegation in Drosophila

Genetics ◽

10.1093/genetics/160.3.995 ◽

2002 ◽

Vol 160 (3) ◽

pp. 995-1009 ◽

Cited By ~ 2

Author(s):

Kathryn M Donaldson ◽

Amy Lui ◽

Gary H Karpen

Keyword(s):

Position Effect ◽

Position Effect Variegation ◽

Yellow Body ◽

Effect Variegation ◽

Different Types ◽

Secondary Analyses ◽

And Function ◽

In Cis ◽

Telomere Structure ◽

Color Gene

Abstract Terminal deletions of a Drosophila minichromosome (Dp(1;f)1187) dramatically increase the position effect variegation (PEV) of a yellow+ body-color gene located in cis. Such terminal deficiency-associated PEV (TDA-PEV) can be suppressed by the presence of a second minichromosome, a phenomenon termed “trans-suppression.” We performed a screen for mutations that modify TDA-PEV and trans-suppression. Seventy suppressors and enhancers of TDA-PEV were identified, but no modifiers of trans-suppression were recovered. Secondary analyses of the effects of these mutations on different PEV types identified 10 mutations that modify only TDA-PEV and 6 mutations that modify TDA-PEV and only one other type of PEV. One mutation, a new allele of Su(var)3-9, affects all forms of PEV, including silencing associated with the insertion of a transgene into telomeric regions (TPE). This Su(var)3-9 allele is the first modifier of PEV to affect TPE and provides a unique link between different types of gene silencing in Drosophila. The remaining mutations affected multiple PEV types, indicating that general PEV modifiers impact TDA-PEV. Modifiers of TDA-PEV may identify proteins that play important roles in general heterochromatin biology, including proteins involved in telomere structure and function and the organization of chromosomes in the interphase nucleus.

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A bacterial position effect: when the F factor in E. coli K12 is integrated in cis to a chromosomal gene that is flanked by IS1 repeats the elements are activated so that amplification and other regulatory changes that affect the gene can occur

Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis ◽

10.1016/0027-5107(91)90082-y ◽

1991 ◽

Vol 248 (1) ◽

pp. 1-15 ◽

Cited By ~ 6

Author(s):

C CLUGSTON ◽

A JESSOP

Keyword(s):

Position Effect ◽

Chromosomal Gene ◽

E Coli ◽

Regulatory Changes ◽

F Factor ◽

In Cis

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Eukaryotic transcription termination factor La mediates transcript release and facilitates reinitiation by RNA polymerase III

Molecular and Cellular Biology ◽

10.1128/mcb.14.3.2147-2158.1994 ◽

1994 ◽

Vol 14 (3) ◽

pp. 2147-2158

Author(s):

R J Maraia ◽

D J Kenan ◽

J D Keene

Keyword(s):

Rna Polymerase ◽

Rna Binding ◽

Transcription Termination ◽

Rna Polymerase Iii ◽

Class Iii ◽

Ample Evidence ◽

Polymerase Iii ◽

Transcription Complexes ◽

Pol Iii

Ample evidence indicates that Alu family interspersed elements retrotranspose via primary transcripts synthesized by RNA polymerase III (pol III) and that this transposition sometimes results in genetic disorders in humans. However, Alu primary transcripts can be processed posttranscriptionally, diverting them away from the transposition pathway. The pol III termination signal of a well-characterized murine B1 (Alu-equivalent) element inhibits RNA 3' processing, thereby stabilizing the putative transposition intermediary. We used an immobilized template-based assay to examine transcription termination by VA1, 7SL, and Alu class III templates and the role of transcript release in the pol III terminator-dependent inhibition of processing of B1-Alu transcripts. We found that the RNA-binding protein La confers this terminator-dependent 3' processing inhibition on transcripts released from the B1-Alu template. Using pure recombinant La protein and affinity-purified transcription complexes, we also demonstrate that La facilitates multiple rounds of transcription reinitiation by pol III. These results illustrate an important role for La in RNA production by demonstrating its ability to clear the termination sites of class III templates, thereby promoting efficient use of transcription complexes by pol III. The role of La as a potential regulatory factor in transcript maturation and how this might apply to Alu interspersed elements is discussed.

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An unusual genomic position effect on Drosophila white gene expression: pairing dependence, interactions with zeste, and molecular analysis of revertants.

Genetics ◽

10.1093/genetics/130.1.125 ◽

1992 ◽

Vol 130 (1) ◽

pp. 125-138 ◽

Cited By ~ 2

Author(s):

T Hazelrigg ◽

S Petersen

Keyword(s):

Gene Expression ◽

Regulatory Element ◽

Position Effect ◽

Insertion Site ◽

White Gene ◽

Chromosome 2 ◽

Wild Type ◽

Gene Copies ◽

In Trans ◽

In Cis

Abstract The white gene in the AR4-24 P[white,rosy] insertion on chromosome 2 has a novel expression pattern, in which it is repressed in the dorsal half of the eye. X-ray mutagenesis led to the isolation of six revertants mapping to chromosome 2, which are wild type in a zeste+ background, and three extreme derivatives, in which white gene expression is repressed in ventral regions of the eye as well. By Southern blot analyses the breakpoints of five of the revertants and one of the extreme derivatives were mapped in the flanking DNA bordering each side of the AR4-24 insertion. The revertants show some dorsal repression of white in the presence of z1, and by this criterion each is only a partial revertant. The extreme derivatives act not only in cis, but also in trans to repress expression of AR4-24 and its various derivatives. We provide evidence that these trans effects are proximity-dependent effects, possibly mediated by pairing of gene copies, as they do not extend to copies of the white gene located elsewhere in the genome. We show that one extreme derivative, E1, is a small deletion spanning the insertion site at the 5' end of the white gene, and propose that the distance between a negative regulatory element in the 5' flanking DNA and the white promoter influences the degree of the repression.

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Expanding heterochromatin reveals discrete subtelomeric domains delimited by chromatin landscape transitions

10.1101/187138 ◽

2017 ◽

Author(s):

Antoine Hocher ◽

Myriam Ruault ◽

Petra Kaferle ◽

Marc Descrimes ◽

Mickael Garnier ◽

...

Keyword(s):

Meta Analysis ◽

Position Effect ◽

Histone Mark ◽

Eukaryotic Genome ◽

Wild Type ◽

Histone Marks ◽

The Core ◽

Defective Mutant ◽

H3k79 Methylation ◽

Subtelomeric Regions

AbstractThe eukaryotic genome is divided into chromosomal domains of heterochromatin and euchromatin. Transcriptionally silent heterochromatin is found at subtelomeric regions, leading to the telomeric position effect (TPE) in yeast, fly and man. Heterochromatin generally initiates and spreads from defined loci, and diverse mechanisms prevent the ectopic spread of heterochromatin into euchromatin. Here, we overexpressed the silencing factor Sir3 at various levels in yeast, and found that Sir3 spreading into Extended Silent Domains (ESD) eventually reached saturation at subtelomeres. We observed that Sir3 spreading into ESDs covered zone associated with specific histone marks in wild-type cells and stopped at zones of histone mark transitions including H3K79 tri-methylation levels. The conserved enzyme Dot1 deposits H3K79 methylation, and we found that it is essential for viability upon overexpression of Sir3, but not of a spreading-defective mutant Sir3A2Q. These data suggest that H3K79 methylation actively blocks Sir3 spreading. Lastly, our meta-analysis uncovers previously uncharacterized discrete subtelomeric domains associated with specific chromatin features offering a new viewpoint on how to separate subtelomeres from the core chromosome.

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