INO80 Chromatin Remodeling Coordinates Metabolic Homeostasis with Cell Division

Abstract

SUMMARY Adaptive survival requires the coordination of nutrient availability with expenditure of cellular resources. For example, in nutrient-limited environments, 50% of all S. cerevisiae genes synchronize and exhibit periodic bursts of expression in coordination with respiration and cell division in the yeast metabolic cycle (YMC). Despite the importance of metabolic and proliferative synchrony, the majority of YMC regulators are currently unknown. Here, we demonstrate that the INO80 chromatin-remodeling complex is required to coordinate respiration and cell division with periodic gene expression. Specifically, INO80 mutants have severe defects in oxygen consumption and promiscuous cell division that is no longer coupled with metabolic status. In mutant cells, chromatin accessibility of periodic genes, including TORC1-responsive genes, is relatively static, concomitant with severely attenuated gene expression. Collectively, these results reveal that the INO80 complex mediates metabolic signaling to chromatin to restrict proliferation to metabolically optimal states.

TORC1 regulates the transcriptional response to glucose and developmental cycle via the Tap42-Sit4-Rrd1/2 pathway in Saccharomyces cerevisiae

“…To validate the RNA-seq data, we first compared the expression of TORC1 targets like DIP5 (Dicarboxylic amino acid permease) and GAP1 (General Amino acid permease) in DMSO-and rapamycin-treated spores after 0', 30', 60' and 120' following transfer to nutrient medium. Expression of TORC1-downregulated genes 19 DIP5 and GAP1 was enhanced by rapamycin treatment after 1 hour following transfer of spores to nutrient medium consistent with RNA-Seq data (Supplementary Figure S9).…”

“…Genes in class VIII (N=804) are not regulated by glucose in wild type but only in pka-as cells and were excluded from further analysis. We compared the remaining list of glucose-responsive genes ( N=2469) with the list of 2426 TORC1 target genes reported in a recent transcriptomic study (14,19). We found that 58 % of glucose-responsive genes (N=1436; upregulated=828 and downregulated =608) were co-regulated by TORC1 ( Figure 3C).…”

“…We compared our list of 1102 TORC1 target genes with the list of TORC1 targets obtained from a microarray analysis-based study (28) and a recent RNA-Seq study (19) both performed with vegetative cells. Only 90 (18%) of the TORC1 targets identified in the microarray-based study (28) were in our set ( Figure S10).…”

“…A) Comparison of our TORC1 target list identified during spore germination with those reported in a Micro-array-based study (Shamji et al (28) ) and an RNA-Seq study (Gowans et al (19)) both performed with vegetative cells. 48 B) Comparison of the list of glucose-responsive genes (Wang et al (14)) with TORC1 target lists identified by our RNA-Seq analysis and an independent RNA-Seq study (Gowans et al) (19).\ Supplementary Figure S11. TORC1 regulates a subset of glucose-responsive genes during spore germination.…”

“…Only 90 (18%) of the TORC1 targets identified in the microarray-based study (28) were in our set ( Figure S10). However, about 935 (84.8%) of the TORC1 targets identified by RNA-Seq (19) were in our target list ( Supplementary Figure S10 ). We don't know the precise reason for differences in the TORC1 targets predicted by microarray and RNA-Seq methods but the differences in sensitivities of the two transcriptomic approaches (29) could be a contributing factor.…”