GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE313nnn/GSE313873/primaryOK200TranscriptomicsCaenorhabditis elegansExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE313873GEOGSEfalseHLH-30/TFEB is necessary for chromatin reorganization and maintenance of cell quiescence during starvation in C. elegansCellular 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.2026/09/21GSE313873GSM9377002GSM9377001GSM9377011GSM9377000GSM9377010GSM9377006GSM9377005GSM9377004GSM9377003GSM9376999GSM9376998GSM9377009GSM9376997GSM9377008GSM9377007GSM937699619757313873Caenorhabditis elegans