Moreno-Rivero, A. | bioRxiv Science

bioRxiv2025

HLH-30/TFEB is necessary for chromatin reorganization and maintenance of cell quiescence during starvation in C. elegans

Cellular quiescence is a metabolically active, non-proliferative state critical for tissue maintenance and regenerative capacity, with broad implications for aging and age-related diseases. In Caenorhabditis elegans, L1 developmental arrest upon hatching in the absence of food provides a robust in vivo model to study quiescence. Here, we investigate the roles of the transcription factors HLH-30/TFEB and DAF-16/FOXO during L1 arrest. We show that HLH-30 and DAF-16 collaborate to ensure survival under starvation, with reciprocal regulation of their subcellular localization and transcriptional activity. HLH-30 exerts broad transcriptional control during L1 arrest, modulating genes involved in chromosome organization and cell cycle progression. Profiling of chromatin spatial distribution reveals that HLH-30 is required for fasting-induced 3D chromatin reorganization. Loss of HLH-30 disrupts seam cell cycle arrest and leads to overactivation of the pioneer transcription factor BLMP-1, leading to premature initiation of developmental programs under starvation. Our findings uncover previously unrecognized functions of HLH-30 in genome architecture and quiescence regulation, highlighting conserved mechanisms of transcriptional control during nutrient deprivation with implications for aging and disease.

developmental biology↗

bioRxiv2024

Desynchronization between timers provokes transient arrest during C. elegans development

In multicellular organisms, development entails the progression of diverse cellular processes that need to be temporally coordinated. During C. elegans postembryonic development, the events of molting and cell divisions progress in parallel during four larval stages and are modulated by external cues such as temperature and nutrient availability. While seam cell divisions occur predominantly before ecdysis of the cuticle, the order of the events can change, suggesting that they are controlled by independent mechanisms. Here, we have analyzed the impact of reduced insulin signaling in molting and in stage-specific cell divisions. We find that reduced insulin signaling in the daf-2(e1370) allele delays both of these events but has a larger impact on the timing of cell divisions, thus increasing the desynchrony between the events. The relative delay in seam cell divisions leads to a delay in the initiation of the subsequent stage of the molting program, providing a mechanism for resynchronization of developmental processes to the beginning of the larval stages.

developmental biology↗