Predominant expression of Sir2α, an NAD-dependent histone deacetylase, in the embryonic mouse heart and brain
Predominant expression of Sir2α, an NAD-dependent histone deacetylase, in the embryonic mouse heart and brain
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DOI：
10.1016/s0014-5793(03)01444-3
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发表时间：
2004-01-02
期刊：
影响因子：
3.5
通讯作者：
Horio, Y
中科院分区：
文献类型：
--
作者：
Sakamoto, J;Miura, T;Horio, Y
Sir 2是一种NAD依赖性组蛋白脱乙酰酶，在酵母中的长寿、基因沉默、异染色质形成、DNA修复和DNA重组抑制中发挥作用。哺乳动物同源物Sir 2alpha（SIRT 1）已被证明能抑制p53依赖性细胞凋亡，但其生理作用仍不清楚。我们发现Sir 2 α在胚胎发生过程中的表达水平很高。早在胚胎d（E）4.5就检测到最高的Sir 2 α mRNA表达。虽然在胚胎发生过程中表达水平下调，但在胚胎后期（E18.5）仍有高水平的表达。在胚胎中，Sir 2alpha在心脏、大脑、脊髓和背根神经节中高水平表达。这些器官中的表达水平在E10.5-E13.5时较高，在E16.5时较低。定量逆转录聚合酶链反应显示，在E12.5和E14.5之间，心脏中Sir 2 α mRNA含量减少了60%。E14.5后，心脏中的表达水平保持恒定，直至27月龄。Sir 2 α蛋白在胚胎心脏中的表达模式与mRNA的表达模式一致。这些结果表明Sir 2 α不仅在早期胚胎发生中，而且在心脏发生和神经发生中具有阶段特异性的新作用。(C)2003年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
Sir2 is an NAD-dependent histone deacetylase that functions in longevity, gene silencing, heterochromatin formation, DNA repair, and suppression of DNA recombination in yeast. The mammalian homolog Sir2alpha (SIRT1) has been shown to inhibit p53-dependent apoptosis, but its physiological roles are still not known. We found that the level of Sir2alpha expression during embryogenesis was high. The highest Sir2alpha mRNA expression was detected as early as embryonic day (E) 4.5. Although the level was down-regulated during embryogenesis, a high level of expression was still found in the late embryonic stage (E18.5). In embryos, Sir2alpha was expressed at high levels in the heart, brain, spinal cord, and dorsal root ganglia. The expression levels in these organs were high on E10.5-E13.5 and low on E16.5. Quantitative reverse transcription polymerase chain reaction showed a 60% reduction in Sir2alpha mRNA content in the heart between E12.5 and E14.5. After E14.5, the expression level in the heart remained constant up to 27 months of age. The expression pattern of Sir2alpha protein in embryonic hearts was consistent with that of mRNA. These results suggest new roles of Sir2alpha not only in early embryogenesis but also in cardiogenesis and neurogenesis with a stage-specific manner. (C) 2003 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.