McKnight G S, Hager L, Palmiter R D
Cell. 1980 Nov;22(2 Pt 2):469-77. doi: 10.1016/0092-8674(80)90357-8.
The short chain aliphatic acid salts, butyrate and propionate, are effective inhibitors of histone deacetylation in chick oviduct at 2--5 mM; they also prevent the hormonal induction of the ovalbumin and transferrin genes. The less potent deacetylase inhibitor isobutyrate is correspondingly less effective in blocking egg white mRNA induction; acetate has little effect at concentrations up to 15 mM. Butyrate does not appear to alter estrogen receptor binding in the nucleus, total RNA synthesis, or protein synthesis during the early hours of treatment when its specific effects on deacetylation and egg white gene transcription are observed. In addition to preventing the induction, butyrate also causes a rapid deinduction when added to preinduced cultures; ovalbumin and transferrin gene transcription decline with a half-life of 15--30 min. The effects of butyrate on egg white mRNA induction and deacetylation are completely reversible, and mRNA induction resumes within 1 hr after removal of butyrate from the medium. These results suggest that the modification of either histones or other unidentified regulatory proteins by acetylation may play a role in the mechanism of estrogen-mediated gene induction.
短链脂肪酸盐，即丁酸盐和丙酸盐，在2 - 5 mM浓度下是鸡输卵管中组蛋白去乙酰化的有效抑制剂；它们还能阻止激素诱导的卵清蛋白和转铁蛋白基因表达。效力较弱的去乙酰化酶抑制剂异丁酸盐在阻断蛋清mRNA诱导方面相应地效果较差；乙酸盐在浓度高达15 mM时几乎没有作用。在观察到丁酸盐对去乙酰化和蛋清基因转录的特定作用的处理早期，它似乎不会改变细胞核中雌激素受体的结合、总RNA合成或蛋白质合成。除了阻止诱导外，丁酸盐添加到预先诱导的培养物中时还会导致快速的去诱导；卵清蛋白和转铁蛋白基因转录以15 - 30分钟的半衰期下降。丁酸盐对蛋清mRNA诱导和去乙酰化的作用是完全可逆的，从培养基中去除丁酸盐后1小时内mRNA诱导恢复。这些结果表明，组蛋白或其他未鉴定的调节蛋白的乙酰化修饰可能在雌激素介导的基因诱导机制中起作用。
