Histone H3 and TORC1 prevent organelle dysfunction and cell death by promoting nuclear retention of HMGB proteins.

Background: How cells respond and adapt to environmental changes, such as nutrient flux, remains poorly understood. Evolutionarily conserved nutrient signaling cascades can regulate chromatin to contribute to genome regulation and cell adaptation, yet how they do so is only now beginning to be elucidated. In this study, we provide evidence in yeast that the conserved nutrient regulated target of rapamycin complex 1 (TORC1) pathway, and the histone H3N-terminus at lysine 37 (H3K37), function collaboratively to restrict specific chromatin-binding high mobility group box (HMGB) proteins to the nucleus to maintain cellular homeostasis and viability.

Saccharomyces cerevisiae TORC1 Controls Histone Acetylation by Signaling Through the Sit4/PP6 Phosphatase to Regulate Sirtuin Deacetylase Nuclear Accumulation.

The epigenome responds to changes in the extracellular environment, yet how this information is transmitted to the epigenetic regulatory machinery is unclear. Using a Saccharomyces cerevisiae yeast model, we demonstrate that target of rapamycin complex 1 (TORC1) signaling, which is activated by nitrogen metabolism and amino acid availability, promotes site-specific acetylation of histone H3 and H4 N-terminal tails by opposing the activity of the sirtuin deacetylases Hst3 and Hst4 TORC1 does so through suppression of the Tap42-regulated Sit4 (PP6) phosphatase complex, as sit4Δ rescues histone acetylation under TORC1-repressive conditions. We further demonstrate that TORC1 inhibition, and subsequent PP6 activation, causes a selective, rapid, nuclear accumulation of Hst4, which correlates with decreased histone acetylation.

Ccr4-not regulates RNA polymerase I transcription and couples nutrient signaling to the control of ribosomal RNA biogenesis.

Ribosomal RNA synthesis is controlled by nutrient signaling through the mechanistic target of rapamycin complex 1 (mTORC1) pathway. mTORC1 regulates ribosomal RNA expression by affecting RNA Polymerase I (Pol I)-dependent transcription of the ribosomal DNA (rDNA) but the mechanisms involved remain obscure. This study provides evidence that the Ccr4-Not complex, which regulates RNA Polymerase II (Pol II) transcription, also functions downstream of mTORC1 to control Pol I activity.

Environmental signaling through the mechanistic target of rapamycin complex 1: mTORC1 goes nuclear.

Mechanistic target of rapamycin complex 1 (mTORC1) is a well-known regulator of cell growth and proliferation in response to environmental stimuli and stressors. To date, the majority of mTORC1 studies have focused on its function as a cytoplasmic effector of translation regulation. However, recent studies have identified additional, nuclear-specific roles for mTORC1 signaling related to transcription of the ribosomal DNA (rDNA) and ribosomal protein (RP) genes, mitotic cell cycle control, and the regulation of epigenetic processes.

Target of rapamycin signaling regulates high mobility group protein association to chromatin, which functions to suppress necrotic cell death.

Background: The target of rapamycin complex 1 (TORC1) is an evolutionarily conserved signal transduction pathway activated by environmental nutrients that regulates gene transcription to control cell growth and proliferation. How TORC1 modulates chromatin structure to control gene expression, however, is largely unknown. Because TORC1 is a major transducer of environmental information, defining this process has critical implications for both understanding environmental effects on epigenetic processes and the role of aberrant TORC1 signaling in many diseases, including cancer, diabetes, and cardiovascular disease.