Predominant expression of Sir2alpha, an NAD-dependent histone deacetylase, in the embryonic mouse heart and brain

Abstract

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.