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Munoz-Barrera, M.* ; Mata-Cabana, A.* ; Moreno-Rivero, A.* ; Piubeli, F.A.* ; Ren-Barroso, B.* ; Al-Refaie, N. ; Gutierrez, G.* ; Cabianca, D.S. ; Olmedo, M.*

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

Nucleic Acids Res. 54:gkag949 (2026)
Publ. Version/Full Text DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Cellular quiescence is a low metabolic, 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 causes the overactivation of the transcription factors BLMP-1 and CEBP-1, which contribute 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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Caenorhabditis-elegans; Stress Resistance; Daf-16; Transcription; Arrest; Family; Cycle; Lin-4; Tfeb
ISSN (print) / ISBN 0305-1048
e-ISSN 1362-4962
Journal Nucleic Acids Research
Quellenangaben Volume: 54, Issue: 18, Pages: , Article Number: gkag949 Supplement: ,
Publisher Oxford University Press
Publishing Place Great Clarendon St, Oxford Ox2 6dp, England
Reviewing status Peer reviewed
Institute(s) Institiute of Functional Epigenetics (IFE)
Grants CBUA-University of Seville
ERDF/EU
University of Sevilla
Scientific Exchange Grants
German Research Foundation