Wang Sue-Hong, Tung Shu-Yun, Su Kuan-Chung, Shen Hsiao-Hsuian, Hong Jia-Yang, Tsai Ming-Shiun, Liou Gunn-Guang
Department of Biomedical Sciences, Chung Shan Medical University, Taichung, Taiwan.
Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
Genes Cells. 2019 Jun;24(6):449-457. doi: 10.1111/gtc.12685. Epub 2019 May 5.
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 preheterochromatin and contributes to the spreading of SIR complexes along the chromatin fiber to form extended silent heterochromatin regions. Here, we show 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 play 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.
为了研究表观遗传基因沉默，酵母是一种出色的模式生物。Sir蛋白是形成沉默异染色质所必需的。Sir2将组蛋白去乙酰化与NAD水解偶联，以生成一种内源性表观遗传代谢小分子O-乙酰-ADP-核糖（AAR）。AAR参与SIR复合物的构象变化，调节SIR-核小体前异染色质的形成，并有助于SIR复合物沿染色质纤维扩散，以形成延伸的沉默异染色质区域。在此，我们表明，在额外添加外源性AAR或AAR代谢酶缺陷的情况下，AAR能够增强染色质沉默效应，但在AAR合成酶缺陷状态下会降低染色质沉默效应。我们的结果提供了AAR生物学功能重要性的证据。这表明AAR不仅在体外起作用，而且在体内也发挥作用，以增强异染色质表观遗传基因沉默的效果。然而，有必要对AAR进行进一步研究，以扩展我们对表观遗传学及相关小分子的认识。
