Lifespan and resistance to heat stress depend on histone biotinylation in Drosophila melanogaster

GABRIELA CAMPOREALE, JOEL C EISSENBERG, ENNIO GIORDANO, JANOS ZEMPLENI

San Francisco, CA - EEUU

Conferencia; Federation of American Societies for Experimental Biology (FASEB); 2006

Histone modifications play important roles in chromatin structure and genomic stability. Histone biotinylation is catalyzed by holocarboxylase synthetase (HCS). Previous studies have shown that biotin deficiency is associated with decreased lifespan in Drosophila melanogaster. Here, we determined whether HCS deficiency in Drosophila melanogaster decreases histone biotinylation, lifespan, and resistance to stress. HCS-deficient flies were generated by germline transformation with the SympUAST dsRNA expression vector, generating HCS-specific siRNA. HCS expression decreased by 85% in response to transformation, as judged by real-time PCR and Western blot analysis. HCS deficiency was associated with decreased histone biotinylation. Lifespan of HCS-deficient male and female flies decreased by 20% and 14%, respectively, compared with wild-type flies. In addition, HCS-deficient flies exhibited a decreased resistance to heat stress (34ºC for 4.5 h): survival of HCS-deficient male and female flies decreased by 79% and 49%, respectively. HCS deficiency did not affect susceptibility to cold stress, suggesting specificity. Collectively, these findings are consistent with the notion that HCS-mediated biotinylation of histones plays a crucial role in Drosophila melanogaster lifespan and stress resistance.