The general control nonderepressible-2 kinase mediates stress response and longevity induced by target of rapamycin inactivation in Caenorhabditis elegans.

The general control nonderepressible 2 (GCN2) kinase is a nutrient-sensing pathway that responds to amino acids deficiency and induces a genetic program to effectively maintain cellular homeostasis. Here we established the conserved role of Caenorhabditis elegans GCN-2 under amino acid limitation as a translation initiation factor 2 (eIF2) kinase. Using a combination of genetic and molecular approaches, we showed that GCN-2 kinase activity plays a central role in survival under nutrient stress and mediates lifespan extension conferred by dietary restriction (DR) or inhibition of the major nutrient-sensing pathway, the target of rapamycin (TOR).

The Tup1 corepressor directs Htz1 deposition at a specific promoter nucleosome marking the GAL1 gene for rapid activation.

The SWR1 complex (SWR1-C)-dependent deposition of the histone variant Htz1 on promoter nucleosomes is typical of Saccharomyces cerevisiae genes whose expression is frequently reprogrammed. Although this epigenetic marking is of significant physiological importance, the determinants of Htz1 deposition, the conditions that set off SWR1-C occupancy, and the implications of Htz1 in transcriptional initiation are issues that remain unresolved. In this report, we addressed these questions by investigating the GAL1 promoter.

Spt3 and Mot1 cooperate in nucleosome remodeling independently of TBP recruitment.

We have investigated the requirements for nucleosome remodeling upon transcriptional induction of the GAL1 promoter. We found that remodeling was dependent on two SAGA complex components, Gcn5 and Spt3. The involvement of the latter was surprising as its function has been suggested to be directly involved in TATA-binding protein (TBP) recruitment.

Post-TATA binding protein recruitment clearance of Gcn5-dependent histone acetylation within promoter nucleosomes.

Transcriptional activation of eukaryotic genes often requires the function of histone acetyltransferases (HATs), which is expected to result in the hyperacetylation of histones within promoter nucleosomes. In this study we show that, in Saccharomyces cerevisiae, the steady-state levels of Gcn5-dependent histone acetylation within a number of transcriptionally active promoters are inversely related to the rate of transcription. High acetylation levels were measured only when transcription was attenuated either by TATA element mutations or in a strain carrying a temperature-sensitive protein component of RNA polymerase II.

Gcn4 occupancy of open reading frame regions results in the recruitment of chromatin-modifying complexes but not the mediator complex.

Eukaryotic transcriptional activators usually recognize short DNA motifs, which are not only located within promoter regions, but also scattered throughout the genome. Assuming that the function of activators at non-promoter regions is wasteful and perhaps harmful, one can ask whether such binding is somehow prevented or if transcription is blocked at a downstream step. Here, we show that the yeast transcriptional activator Gcn4 is associated in vivo with several non-promoter euchromatic sites.