Changes in histone modifications are an attractive model through which environmental signals, such as diet, could be integrated in the cell for regulating its lifespan. However, evidence linking dietary interventions with specific alterations in histone modifications that subsequently affect lifespan remains elusive. We show here that deletion of histone N-alpha-terminal acetyltransferase Nat4 and loss of its associated H4 N-terminal acetylation (N-acH4) extend yeast replicative lifespan. Notably, nat4Δ-induced longevity is epistatic to the effects of calorie restriction (CR). Consistent with this, (i) Nat4 expression is downregulated and the levels of N-acH4 within chromatin are reduced upon CR, (ii) constitutive expression of Nat4 and maintenance of N-acH4 levels reduces the extension of lifespan mediated by CR, and (iii) transcriptome analysis indicates that nat4Δ largely mimics the effects of CR, especially in the induction of stress-response genes. We further show that nicotinamidase Pnc1, which is typically upregulated under CR, is required for nat4Δ-mediated longevity. Collectively, these findings establish histone N-acH4 as a regulator of cellular lifespan that links CR to increased stress resistance and longevity.

• Klíčová slova
• Nat4, Pnc1, calorie restriction, histone N‐terminal acetylation, lifespan,
• MeSH
• acetylace MeSH
• aktivace transkripce MeSH
• časové faktory MeSH
• chromatin metabolismus   MeSH
• dlouhověkost MeSH
• down regulace MeSH
• histonacetyltransferasy metabolismus   MeSH
• histony metabolismus   MeSH
• kalorická restrikce * MeSH
• N-terminální acetyltransferasa D nedostatek   genetika   fyziologie   MeSH
• nikotinamidasa genetika   metabolismus   MeSH
• posttranslační úpravy proteinů MeSH
• regulace genové exprese u hub * MeSH
• Saccharomyces cerevisiae - proteiny genetika   metabolismus   fyziologie   MeSH
• Saccharomyces cerevisiae genetika   fyziologie   MeSH
• stanovení celkové genové exprese MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• chromatin MeSH
• histonacetyltransferasy MeSH
• histony MeSH
• N-terminální acetyltransferasa D MeSH
• NAT4 protein, S cerevisiae MeSH Prohlížeč
• nikotinamidasa MeSH
• PNC1 protein, S cerevisiae MeSH Prohlížeč
• Saccharomyces cerevisiae - proteiny MeSH

• MeSH
• kouření * MeSH
• lidé MeSH
• medicína založená na důkazech MeSH
• nikotinamidasa MeSH
• odvykání kouření * MeSH
• prevence kouření MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• kongresy MeSH
• Názvy látek
• nikotinamidasa MeSH

It was the aim of the present communication to find a simple test for a reliable discrimination of Mycobacterium bovis BCG from Mycobacterium tuberculosis. A total of 26 BCG strains, out of them 10 Czechoslovak strains (2 lyophilized cultures of BCG of different batch, 6 strains isolated from abscesses of children after BCG-vaccination and 2 strains from fatal cases after BCG-vaccination) and 16 strains obtained from foreign laboratories, were used. Of the tested characteristics a combination of 3 tests, sensitivity to 1 microgram of 2-thiophene carbonylhydrazide (TCH), activity of 3 acylamidases (urease, nicotinamidase and pyrazinamidase) and a quantitative nitrate test, was found to be most advantageous. The Czechoslovak strains of Mycobacterium bovis BCG were fully sensitive to TCH, of the 3 acylamidases mentioned above only urease was positive and nitrate was reduced only little or not at all. On the other hand, strains of Mycobacterium tuberculosis were always resistant to TCH, had positive urease, nicotinamidase and pyrazinamidase and reduced nitrate very intensively.

• MeSH
• antituberkulotika farmakologie   MeSH
• azidy farmakologie   MeSH
• BCG vakcína * MeSH
• dítě MeSH
• králíci MeSH
• kultivační média MeSH
• lidé MeSH
• morčata MeSH
• Mycobacterium bovis účinky léků   enzymologie   MeSH
• nikotinamidasa metabolismus   MeSH
• předškolní dítě MeSH
• ureasa metabolismus   MeSH
• zvířata MeSH
• Check Tag
• dítě MeSH
• králíci MeSH
• lidé MeSH
• morčata MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antituberkulotika MeSH
• azidy MeSH
• BCG vakcína * MeSH
• kultivační média MeSH
• nikotinamidasa MeSH
• ureasa MeSH