State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, 400715, China.
Chongqing Engineering and Technology Research Center for Novel Silk Materials, Southwest University, 2, Tiansheng Road, Beibei, Chongqing, 400715, China.
Epigenetics Chromatin. 2018 Aug 27;11(1):48. doi: 10.1186/s13072-018-0216-y.
The silkworm, Bombyx mori, a typical representative of metamorphic insects, is of great agricultural and economic importance. The steroid hormone ecdysone (20-hydroxyecdysone, 20E) is the central regulator of insect developmental transitions, and its nuclear receptors are crucial for numerous biological processes, including reproduction, metabolism, and immunity. However, genome-wide DNA regulatory elements and the ecdysone receptor (EcR) that control these programs of gene expression are not well defined.
In this study, we investigated the alterations in three types of histone modification in silkworm embryonic cells treated with 20E by chromatin immunoprecipitation sequencing (ChIP-seq). We identified enhancers using histone modifications and derived genome-wide ecdysone-dependent enhancer activity maps in the silkworm. We found enhancers enriched for monomethylation of histone H3 Lys4 (H3K4me1) that showed dynamic changes in acetylation of histone H3 Lys27 (H3K27ac) after 20E treatment and functioned to regulate the transcription of specific genes. EcR regulated transcription by binding not only to proximal promoters but also to the distal enhancers of target genes. Moreover, only 52.65% EcR peaks contained ecdysone response element (EcRE) motif, suggesting that EcR regulates the expression of target genes not only by binding directly to EcRE, but also by binding with other transcription factor.
Our findings provide novel insights into the complex regulatory landscape of hormone-responsive cell activity and a basis for understanding the complex transcriptional regulatory processes of ecdysone.
家蚕是变态昆虫的典型代表，具有重要的农业和经济价值。蜕皮激素（20-羟基蜕皮酮，20E）是昆虫发育转变的中心调节剂，其核受体对于许多生物学过程至关重要，包括生殖、代谢和免疫。然而，基因组范围的 DNA 调控元件和调控这些基因表达程序的蜕皮激素受体（EcR）尚未得到很好的定义。
在这项研究中，我们通过染色质免疫沉淀测序（ChIP-seq）研究了 20E 处理的家蚕胚胎细胞中三种组蛋白修饰的变化。我们使用组蛋白修饰鉴定了增强子，并在家蚕中得出了全基因组蜕皮激素依赖性增强子活性图谱。我们发现增强子富含组蛋白 H3 赖氨酸 4 的单甲基化（H3K4me1），20E 处理后 H3 赖氨酸 27 的乙酰化（H3K27ac）呈现动态变化，可调节特定基因的转录。EcR 通过结合不仅近端启动子，还结合靶基因的远端增强子来调节转录。此外，只有 52.65%的 EcR 峰含有蜕皮激素反应元件（EcRE）基序，这表明 EcR 调节靶基因的表达不仅通过直接结合 EcRE，还通过与其他转录因子结合。
我们的研究结果提供了激素反应细胞活性的复杂调控景观的新见解，并为理解蜕皮激素的复杂转录调控过程提供了基础。
