Glucocorticoid and other adipogenic hormones are secreted in mammals in circadian oscillations. Loss of this circadian oscillation pattern correlates with obesity in humans, raising the intriguing question of how hormone secretion dynamics affect adipocyte differentiation. Using live, single-cell imaging of the key adipogenic transcription factors CEBPB and PPARG, endogenously tagged with fluorescent proteins, we show that pulsatile circadian hormone stimuli are rejected by the adipocyte differentiation control system. In striking contrast, equally strong persistent signals trigger maximal differentiation. We identify the mechanism of how hormone oscillations are filtered as a combination of slow and fast positive feedback centered on PPARG. Furthermore, we confirm in mice that flattening of daily glucocorticoid oscillations significantly increases the mass of subcutaneous and visceral fat pads. Together, our study provides a molecular mechanism for why stress, Cushing's disease, and other conditions for which glucocorticoid secretion loses its pulsatility may lead to obesity.

The analysis of large-scale transposon mutant libraries is becoming a method of choice for functional genomics in bacte The analysis of large-scale transposon mutant libraries is becoming a method of choice for functional genomics in bacte-ria and fungi. We previously established SAturated Transposon Analysis in Yeast (SATAY) to uncover genes necessary for ria and fungi. We previously established SAturated Transposon Analysis in Yeast (SATAY) to uncover genes necessary for growth in any condition in growth in any condition in S. cerevisiae S. cerevisiae (Michel et al., 2017) (Michel et al., 2017. We present an improved version leveraging homologous re . We present an improved version leveraging homologous re-combination to increase transposition efficiency by a factor 10, allowing a single experimenter to rapidly perform several combination to increase transposition efficiency by a factor 10, allowing a single experimenter to rapidly perform several parallel screens. We demonstrate its potential by presenting (1) a comparison of the essential gene sets between two yeast parallel screens. We demonstrate its potential by presenting (1) a comparison of the essential gene sets between two yeast laboratory backgrounds, (2) a comprehensive description of essential genes displaying phenotypic delays -we highlight laboratory backgrounds, (2) a comprehensive description of essential genes displaying phenotypic delays -we highlight their common features and propose plausible explanations for this phenomenon -, (3) a genome-wide analysis of loss-their common features and propose plausible explanations for this phenomenon -, (3) a genome-wide analysis of lossand gain-of-function mutations conferring sensitivity or resistance to a compendium of 9 anti-fungal compounds. This and gain-of-function mutations conferring sensitivity or resistance to a compendium of 9 anti-fungal compounds. This study highlights the power of this improved SATAY protocol for yeast functional-and pharmaco-genomics. study highlights the power of this improved SATAY protocol for yeast functional-and pharmaco-genomics.