Department of Biochemistry and Molecular Biology, University of Szeged, Szeged, Hungary.
PLoS One. 2012;7(7):e40565. doi: 10.1371/journal.pone.0040565. Epub 2012 Jul 10.
Posttranslational modification of histones regulates transcription but the exact role that acetylation of specific lysine residues plays in biological processes in vivo is still not clearly understood. To assess the contribution of different histone modifications to transcriptional activation in vivo, we determined the acetylation patterns on the ecdysone induced Eip74EF and Eip75B genes in Drosophila melanogaster larvae by chromatin immunoprecipitation. We found that acetylation of histone H3 lysine 23 is localized to promoters and correlates with endogenous ecdysone induced gene activation. In contrast, acetylation of lysines 8, 12 and 16 of histone H4 and lysine 9 of histone H3 showed minor differences in their distribution on the regulatory and transcribed regions tested, and had limited or no correlation with ecdysone induced transcriptional activity. We found that dCBP, which is encoded by the nejire gene, acetylates H3 lysine 23 in vivo, and silencing of nejire leads to reduced expression of the Eip74EF and Eip75B genes. Our results suggest that acetylation of specific lysine residues of histones contribute specifically to the dynamic regulation of transcription. Furthermore, along with previous studies identify CBP dependent H3 lysine 23 acetylation as an evolutionarily conserved chromatin modification involved in steroid induced gene activation.
组蛋白的翻译后修饰调节转录，但乙酰化特定赖氨酸残基在体内生物过程中的确切作用仍不清楚。为了评估不同组蛋白修饰对体内转录激活的贡献，我们通过染色质免疫沉淀法确定了黑腹果蝇幼虫中蜕皮激素诱导的 Eip74EF 和 Eip75B 基因的组蛋白 H3 赖氨酸 23 的乙酰化模式。我们发现组蛋白 H3 赖氨酸 23 的乙酰化定位于启动子处，并与内源性蜕皮激素诱导的基因激活相关。相比之下，组蛋白 H4 的赖氨酸 8、12 和 16 以及组蛋白 H3 的赖氨酸 9 的乙酰化在受测试的调控区和转录区的分布上差异较小，与蜕皮激素诱导的转录活性相关性有限或没有。我们发现，由 nejire 基因编码的 dCBP 在体内乙酰化 H3 赖氨酸 23，而 nejire 的沉默导致 Eip74EF 和 Eip75B 基因的表达减少。我们的结果表明，组蛋白特定赖氨酸残基的乙酰化特异性地有助于转录的动态调节。此外，与之前的研究一起确定了 CBP 依赖性 H3 赖氨酸 23 乙酰化为参与甾体激素诱导基因激活的进化保守的染色质修饰。
