Almouzni G, Khochbin S, Dimitrov S, Wolffe A P
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, NIH, Bethesda, Maryland 20892.
Dev Biol. 1994 Oct;165(2):654-69. doi: 10.1006/dbio.1994.1283.
We examine the potential role of histone hyperacetylation in gene activation during Xenopus development using Trichostatin A, (TSA), a specific inhibitor of histone deacetylase. We find that TSA is very effective in inducing both core histone hyperacetylation and histone H1(0) gene expression in a Xenopus somatic cell line. In contrast, TSA does not induce histone hyperacetylation or histone H1(0) transcription in Xenopus oocytes. Histone hyperacetylation is developmentally regulated during Xenopus embryogenesis; hyperacetylated histones first accumulate early in gastrulation. The capacity of TSA to induce histone H1(0) gene expression correlates with the induction of histone hyperacetylation. Concentrations of TSA sufficient to induce histone hyperacetylation in Xenopus embryos delay gastrulation and cause diminished midtrunk and posterior formation, suggesting defects in mesoderm formation. Although the constitutive hyperacetylation of the histones does not prevent either the cell division or differentiation sufficient for early morphogenesis it has a role in establishing stable states of differential gene activity during gastrulation.
我们使用曲古抑菌素A（TSA），一种组蛋白去乙酰化酶的特异性抑制剂，来研究组蛋白高度乙酰化在非洲爪蟾发育过程中基因激活方面的潜在作用。我们发现TSA在诱导非洲爪蟾体细胞系中的核心组蛋白高度乙酰化和组蛋白H1(0)基因表达方面非常有效。相比之下，TSA在非洲爪蟾卵母细胞中不会诱导组蛋白高度乙酰化或组蛋白H1(0)转录。组蛋白高度乙酰化在非洲爪蟾胚胎发生过程中受到发育调控；高度乙酰化的组蛋白最早在原肠胚形成早期积累。TSA诱导组蛋白H1(0)基因表达的能力与组蛋白高度乙酰化的诱导相关。在非洲爪蟾胚胎中足以诱导组蛋白高度乙酰化的TSA浓度会延迟原肠胚形成，并导致中躯干和后部形成减少，提示中胚层形成存在缺陷。尽管组蛋白的组成型高度乙酰化并不妨碍早期形态发生所需的细胞分裂或分化，但它在原肠胚形成过程中建立差异基因活性的稳定状态方面发挥作用。
