Heat stress induced Cup9 dependent transcriptional regulation of Sir2
Shyamasree Laskar,Sheeba K,Mrinal Kanti Bhattacharyya,Achuthsankar S. Nair,Pawan K. Dhar,Sunanda Bhattacharyya +5 more
TLDR
The mechanism by which Sir2 is regulated under heat stress is demonstrated, which reveals that a transient heat shock causes a drastic reduction in the SIR2 transcript which results in sustained failure to initiate silencing for as long as 90 generations.Abstract:
The epigenetic writer Sir2 maintains the heterochromatin state of chromosome in three chromosomal regions, namely, the silent mating type loci, telomeres, and the ribosomal DNA (rDNA). In this study, we demonstrated the mechanism by which Sir2 is regulated under heat stress. Our study reveals that a transient heat shock causes a drastic reduction in the SIR2 transcript which results in sustained failure to initiate silencing for as long as 90 generations. Hsp82 overexpression, which is the usual outcome of heat shock treatment, leads to a similar downregulation of SIR2 transcription. Using a series of genetic experiments, we have established that heat shock or Hsp82 overexpression causes upregulation of CUP9 that, in turn, represses SIR2 transcription by binding to its upstream activator sequence. We have mapped the cis regulatory element of SIR2. Our study shows that the deletion of cup9 causes reversal of the Hsp82 overexpression phenotype and upregulation of SIR2 expression in heat-induced Hsp82-overexpressing cells. On the other hand, we found that Cup9 overexpression represses SIR2 transcription and leads to a failure in the establishment of heterochromatin. The results of our study highlight the mechanism by which environmental factors amend the epigenetic configuration of chromatin.read more
Citations
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Hsp90, the concertmaster: tuning transcription.
TL;DR: The role of Hsp90 is discussed in all the three aforementioned mechanisms of transcriptional control, taking examples from various model organisms with a special emphasis on cancer progression.
Quantitative Analysis of Hsp90-Client Interactions Reveals Principles of Substrate Recognition
Mikko Taipale,Irina Krykbaeva,Martina Koeva,Can Kayatekin,Kenneth D. Westover,Georgios I. Karras,Susan Lindquist,Susan Lindquist +7 more
TL;DR: The results establish HSP90 client recognition as a combinatorial process: CDC37 provides recognition of the kinase family, whereas thermodynamic parameters determine client binding within the family.
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Yeast epigenetics: the inheritance of histone modification states.
Callum J O'Kane,Edel M. Hyland +1 more
TL;DR: The recent advancements that for the first time provide a mechanistic understanding of how heterochromatin, dictated by histone modifications specifically, is preserved during S-phase are discussed.
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Hsp90 induces increased genomic instability toward DNA-damaging agents by tuning down RAD53 transcription.
TL;DR: The model organism Saccharomyces cerevisiae is used to establish that a transient heat shock and particularly the concomitant induction of Hsp90 lead to increased genomic instability via transcriptional regulation of the major checkpoint kinase Rad53.
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Double strand breaks may be a missing link between entropy and aging.
TL;DR: This work proposes a new model where the increase of entropy leads to the formation of double strand breaks, resulting in an aging phenotype, which not only offers a new perspective on aging research and facilitates experimental validation, but could also serve as a useful explanatory tool.
References
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Acetylation of the Yeast Histone H4 N Terminus Regulates Its Binding to Heterochromatin Protein SIR3
TL;DR: By affecting SIR3-H4 binding, acetylation may regulate the formation of heterochromatin and help explain the hypoacetylated state of histone H4 in heterochromaatin of eukaryotes.
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Otto G. Berg,Peter H. von Hippel +1 more
TL;DR: The current state of the understanding of structural, thermodynamic and statistical rules that govern the binding of regulatory proteins to functional sites on the DNA genome are summarized here.
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Nicotinamide Clearance by Pnc1 Directly Regulates Sir2-Mediated Silencing and Longevity
TL;DR: Pnc1 positively regulates Sir2-mediated silencing and longevity by preventing the accumulation of intracellular NAM during times of stress, and shows that stress suppresses the inhibitory effect of NAM through the induction of PNC1 expression.
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Chaperoning steroid hormone action
TL;DR: This review discusses the complexities of the chaperone machinery and the diversity of regulatory options afforded by this assistance for hormone action.
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Sir2 deacetylates histone H3 lysine 56 to regulate telomeric heterochromatin structure in yeast.
TL;DR: In vitro and in vivo data indicate that Sir2 deacetylates K56 directly in telomeric heterochromatin to compact chromatin and prevent access to RNA polymerase and ectopic bacterial dam methylase.