Chromatin assembly factor-1 (CAF-1) chaperone regulates Cse4 deposition into chromatin in budding yeast

Hewawasam, Geetha S.; Dhatchinamoorthy, Karthik; Mattingly, Mark; Seidel, Chris; Gerton, Jennifer L.

doi:10.1093/nar/gky405

Cited by 12 publications

(14 citation statements)

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“…That these authors failed to detect Cse4 mislocalization in the hir1D single mutant could be explained by the fact that they assayed a tagged Cse4 allele expressed at endogenous levels, while in our experiments Cse4 was overexpressed. Notably, a recent study under conditions of Cse4 overexpression showed that cac1D reduces Cse4 chromatin deposition genome-wide and suppresses the SDL of psh1D (Hewawasam et al 2018), effects opposite to that observed under the experimental conditions of Lopes da Rosa et al (2011). We do not rule out a role for the HIR complex in mediating removal of Cse4 at extrachromosomal sites; however, our results indicate additional functions of HIR in regulating proteolysis of Cse4 independently of the CAF-1 complex.…”

Section: Discussioncontrasting

confidence: 99%

“…Deletion of CAC2 has been shown to reduce the deposition of overexpressed Cse4 at promoters of medium to highly expressed genes and to suppress the SDL of a psh1D GALCSE4 strain (Hewawasam et al 2018). Our results showed that deletion of CAC2 does not suppress the SDL of hir2D GALCSE4 (Figure 3B); therefore, we hypothesized that deletion of CAC2 would not affect enrichment of Cse4 at promoter regions in the hir2D strain.…”

Section: Mislocalized Cse4 Is Enriched At Promoter Regions In Hir2d Strainsmentioning

confidence: 71%

“…While compromised Psh1-mediated proteolysis contributes in part to the increased stability of Cse4 in hir2D strains, several lines of evidence support additional, Psh1-independent roles for Hir2 in Cse4 proteolysis. As mentioned above, deletion of Cac2, a component of CAF-1, reduces the deposition of Cse4 into chromatin in a psh1D mutant and suppresses the SDL phenotype of a psh1D GALCSE4 strain (Hewawasam et al 2018); however, deletion of Cac2 does not suppress the SDL of hir2D GALCSE4 or mislocalization of Cse4 in a hir2D strain. Second, overexpression of UBI4 can suppress the SDL of psh1D GALCSE4 as we previously reported (Au et al 2013; Figure S5), but overexpression of UBI4 does not suppress the SDL of hir2D GALCSE4 and hir2D psh1D GALCSE4 strains (Figure S5).…”

Section: Discussionmentioning

confidence: 88%

“…The role of Psh1 in proteolysis of Cse4 has been characterized in detail, and these studies have shown that the interactions of Psh1 with Spt16, a component of the FACT (facilitates chromatin transcription/transactions) complex, and casein kinase 2 (CKA2) regulate Cse4 proteolysis (Hewawasam et al 2010(Hewawasam et al , 2014Ranjitkar et al 2010;Au et al 2013;Deyter and Biggins 2014). Recent studies have shown that chromatin assembly factor-1 (CAF-1) promotes the deposition of Cse4 at noncentromeric regions in psh1D mutants, and deletion of Cac2, a component of CAF-1, rescues the lethality of psh1D or cka2D strains overexpressing Cse4 (Hewawasam et al 2018). While the centromere-targeting domain (CATD) in the C-terminus of Cse4 interacts with Psh1, the N-terminus of Cse4 is also required for Cse4 proteolysis (Hewawasam et al 2010;Ranjitkar et al 2010;Au et al 2013).…”

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confidence: 99%

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A Genome-Wide Screen Reveals a Role for the HIR Histone Chaperone Complex in Preventing Mislocalization of Budding Yeast CENP-A

Ciftci-Yilmaz

Mishra

et al. 2018

Genetics

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Centromeric localization of the evolutionarily conserved centromere-specific histone H3 variant CENP-A (Cse4 in yeast) is essential for faithful chromosome segregation. Overexpression and mislocalization of CENP-A lead to chromosome segregation defects in yeast, flies, and human cells. Overexpression of CENP-A has been observed in human cancers; however, the molecular mechanisms preventing CENP-A mislocalization are not fully understood. Here, we used a genome-wide synthetic genetic array (SGA) to identify gene deletions that exhibit synthetic dosage lethality (SDL) when Cse4 is overexpressed. Deletion for genes encoding the replication-independent histone chaperone HIR complex (, ,, ) and a Cse4-specific E3 ubiquitin ligase,, showed highest SDL. We defined a role for Hir2 in proteolysis of Cse4 that prevents mislocalization of Cse4 to noncentromeric regions for genome stability. Hir2 interacts with Cse4 , and strains exhibit defects in Cse4 proteolysis and stabilization of chromatin-bound Cse4 Mislocalization of Cse4 to noncentromeric regions with a preferential enrichment at promoter regions was observed in strains. We determined that Hir2 facilitates the interaction of Cse4 with Psh1, and that defects in Psh1-mediated proteolysis contribute to increased Cse4 stability and mislocalization of Cse4 in the strain. In summary, our genome-wide screen provides insights into pathways that regulate proteolysis of Cse4 and defines a novel role for the HIR complex in preventing mislocalization of Cse4 by facilitating proteolysis of Cse4, thereby promoting genome stability.

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Section: Discussioncontrasting

confidence: 99%

Section: Mislocalized Cse4 Is Enriched At Promoter Regions In Hir2d Strainsmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 88%

mentioning

confidence: 99%

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A Genome-Wide Screen Reveals a Role for the HIR Histone Chaperone Complex in Preventing Mislocalization of Budding Yeast CENP-A

Ciftci-Yilmaz

Mishra

et al. 2018

Genetics

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“…Significance was determined with a Student’s t-test. RNA-seq data was obtained from Hewawasam et al, 2018 . …”

Section: Resultsmentioning

confidence: 99%

Transcription elongation is finely tuned by dozens of regulatory factors

Couvillion

Harlen

Lachance

et al. 2022

eLife

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Understanding the complex network that regulates transcription elongation requires the quantitative analysis of RNA polymerase II (Pol II) activity in a wide variety of regulatory environments. We performed native elongating transcript sequencing (NET-seq) in 41 strains of S. cerevisiae lacking known elongation regulators, including RNA processing factors, transcription elongation factors, chromatin modifiers, and remodelers. We found that the opposing effects of these factors balance transcription elongation and antisense transcription. Different sets of factors tightly regulate Pol II progression across gene bodies so that Pol II density peaks at key points of RNA processing. These regulators control where Pol II pauses with each obscuring large numbers of potential pause sites that are primarily determined by DNA sequence and shape. Antisense transcription varies highly across the regulatory landscapes analyzed, but antisense transcription in itself does not affect sense transcription at the same locus. Our findings collectively show that a diverse array of factors regulate transcription elongation by precisely balancing Pol II activity.

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Unraveling CAF-1 family in Plasmodium falciparum: comparative genome-wide identification and phylogenetic analysis among eukaryotes, expression profiling and protein–protein interaction studies

et al. 2020

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Chromatin assembly factor-1 (CAF-1) chaperone regulates Cse4 deposition into chromatin in budding yeast

Cited by 12 publications

References 0 publications

A Genome-Wide Screen Reveals a Role for the HIR Histone Chaperone Complex in Preventing Mislocalization of Budding Yeast CENP-A

A Genome-Wide Screen Reveals a Role for the HIR Histone Chaperone Complex in Preventing Mislocalization of Budding Yeast CENP-A

Transcription elongation is finely tuned by dozens of regulatory factors

Unraveling CAF-1 family in Plasmodium falciparum: comparative genome-wide identification and phylogenetic analysis among eukaryotes, expression profiling and protein–protein interaction studies

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