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Phosphorylation at serine 28 and acetylation at lysine 9 of histone H3 induced by trichostatin A

机译:曲古抑菌素A诱导组蛋白H3的丝氨酸28磷酸化和赖氨酸9乙酰化。

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Trichostatin A (TSA), a histone deacetylase inhibitor, strongly increases acetylation of the N-terminal tails of histone H3. Many studies have correlated the function of TSA with the hyperacetylation of histone. Although histone H3 is known to be phosphorylated, the effect of acetylation on phosphorylation is not known. Here, we report that in JB6 cells, TSA induces both acetylation at lysine 9 and phosphorylation at serine 28 of histone H3. UVB irradiation, which is known to induce phosphorylation at serine 28, did not significantly affect phosphorylation of histone H3 in TSA-pretreated JB6 cells. In contrast, TSA markedly increased phosphorylation and acetylation of histone H3 in UVB-pretreated JB6 cells. TSA strongly activated MAP kinases. Moreover, PD98059 and SB202190 inhibited TSA-induced phosphorylation but not acetylation of histone H3. Dominant negative mutant ERK2 and dominant negative mutant p38 kinase blocked TSA-stimulated phosphorylation of histone H3 at serine 28. The results indicate that TSA-induced phosphorylation of histone H3 at serine 28 occurs through activation of the MAP kinase pathway and phosphorylated histone H3 is more sensitive to TSA-induced hyperacetylation. The facilitation of phosphorylation and acetylation of histone H3 induced by TSA may play a critical regulatory role in chromatin remodeling and gene expression.
机译:组蛋白脱乙酰基酶抑制剂曲古抑菌素A(TSA)会强烈增强组蛋白H3 N末端尾巴的乙酰化作用。许多研究已经将TSA的功能与组蛋白的高度乙酰化相​​关联。尽管已知组蛋白H3被磷酸化,但是乙酰化对磷酸化的作用是未知的。在这里,我们报道在JB6细胞中,TSA既诱导组蛋白H3的赖氨酸9的乙酰化,又诱导组氨酸H3的丝氨酸28的磷酸化。已知可在丝氨酸28处诱导磷酸化的UVB辐射并未显着影响TSA预处理的JB6细胞中组蛋白H3的磷酸化。相反,TSA显着增加了UVB预处理的JB6细胞中组蛋白H3的磷酸化和乙酰化。 TSA强烈激活了MAP激酶。此外,PD98059和SB202190抑制TSA诱导的组蛋白H3的磷酸化,但不抑制其乙酰化。显性负突变ERK2和显性负突变p38激酶阻断了TSA刺激丝氨酸28处组蛋白H3的磷酸化。结果表明,TSA诱导丝氨酸28处组蛋白H3的磷酸化通过MAP激酶途径的激活而发生,而磷酸化组蛋白H3则更多。对TSA诱导的过度乙酰化敏感。 TSA诱导的组蛋白H3的磷酸化和乙酰化的促进可能在染色质重塑和基因表达中起关键的调节作用。

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