Heat stress induced Cup9 dependent transcriptional regulation of Sir2
TL;DR: 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.
Cites background or methods from "Heat stress induced Cup9 dependent ..."
...was then cross-linked with 1% formaldehyde at 30C for 15 minutes and the experiment was performed as mentioned earlier (Laskar et al., 2014)....
...It modulates the activity of chromatin modifiers and thereby alters gene expression (Laskar et al., 2011; Laskar et al., 2014; Tariq et al., 2009; Khurana and Bhattacharyya, 2015)....
"Heat stress induced Cup9 dependent ..." refers background in this paper
...Sir2 deacetylates histone H3 (at K9, K14, and K56) and H4 (particularly K16) to regulate telomeric heterochromatin structure in yeast (3, 4)....
"Heat stress induced Cup9 dependent ..." refers methods in this paper
...The transcription factors from both the databases TRANSFAC (36) and JASPAR (37), with their ranks, are shown in Table 3....
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