Enhancer role of a native metabolite, O-acetyl-ADP-ribose, on the Saccharomyces cerevisiae chromatin epigenetic gene silencing.

To study the epigenetic gene silencing, yeast is an excellent model organism. Sir proteins are required for the formation of silent heterochromatin. Sir2 couples histone deacetylation and NAD hydrolysis to generate an endogenous epigenetic metabolic small molecule, O-acetyl-ADP-ribose (AAR). AAR is involved in the conformational change of SIR complexes, modulates the formation of SIR-nucleosome pre-heterochromatin and contribute to the spreading of SIR complexes along the chromatin fiber to form extended silent heterochromatin regions. Here, we demonstrate that AAR is capable of enhancing the chromatin silencing effect under either an extra exogenous AAR, or a defect AAR metabolic enzyme situation, but decreasing the chromatin silencing effect under a defect AAR synthetic enzyme state. Our results provide an evidence of biological function importance of AAR. It is indicated that AAR does not only function in vitro but also plays a role in vivo to increase the effect of heterochromatin epigenetic gene silencing. However, further investigations of AAR are warranted to expand our knowledge of epigenetics and associated small molecules. This article is protected by copyright. All rights reserved.