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Sci Adv. 2019 Jul 10;5(7):eaav1165. doi: 10.1126/sciadv.aav1165. eCollection 2019 Jul.

Cellular response to moderate chromatin architectural defects promotes longevity.

Author information

1
Department of Molecular and Human Genetics, and Huffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USA.
2
Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA.

Abstract

Changes in chromatin organization occur during aging. Overexpression of histones partially alleviates these changes and promotes longevity. We report that deletion of the histone H3-H4 minor locus HHT1-HHF1 extended the replicative life span of Saccharomyces cerevisiae. This longevity effect was mediated through TOR signaling inhibition. We present evidence for evolutionarily conserved transcriptional and phenotypic responses to defects in chromatin structure, collectively termed the chromatin architectural defect (CAD) response. Promoters of the CAD response genes were sensitive to histone dosage, with HHT1-HHF1 deletion, nucleosome occupancy was reduced at these promoters allowing transcriptional activation induced by stress response transcription factors Msn2 and Gis1, both of which were required for the life-span extension of hht1-hhf1Δ. Therefore, we conclude that the CAD response induced by moderate chromatin defects promotes longevity.

PMID:
31309140
PMCID:
PMC6620092
DOI:
10.1126/sciadv.aav1165

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