HTZ-1/H2A.Z expression sustains transcriptional programs that regulate Caenorhabditis elegans lifespan.

Authors

Beijia Xie, Enzo Scifo, Ioanna-Maria Menegatou, Rossella Erminia Ciliberti, Mrityunjoy Mondal, Yiru Wang, Antonia Piazzesi, Jialu Hu, Elena De Domenico, Stefan Paulusch, Diego De Stefani, Matthias Schmid, Dagmar Wachten, Marc D Beyer, Pierluigi Nicotera, Nasir Ahmad Aziz, Dan Ehninger, Daniele Bano

Published in

Mechanisms of ageing and development. Pages 112217. Jun 24, 2026. Epub Jun 24, 2026.

Abstract

Animal lifespan depends on coordinated gene expression networks that regulate metabolic adaptation, proteostasis, and stress resilience in response to environmental challenges. Histone variants are key regulators of chromatin dynamics, orchestrating nucleosome remodeling, DNA accessibility, and gene expression. While the role of histone H3.3 in aging and animal survival has been explored across model systems, the contribution of other replication-independent histone variants remains less well-defined. Here, we demonstrate that the evolutionarily conserved histone variant HTZ-1/H2A.Z is essential for organismal survival. In the nematode Caenorhabditis elegans, loss of HTZ-1/H2A.Z disrupts gene expression programs associated with longevity, including those activated in insulin/IGF-1 deficient daf-2 mutants and in mitochondrial Complex I deficient animals. Together, our findings show that HTZ-1/H2A.Z regulates gene expression programs that coordinate metabolic and proteostatic pathways, thereby fine-tuning stress responses and promoting lifespan in animals.

PMID:
42342133
Bibliographic data and abstract were imported from PubMed on 25 Jun 2026.

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