State Key Laboratory of Silkworm Genome Biology, Biological Science Research Center, Southwest University, Chongqing 400715, China.
Chongqing Key Laboratory of Sericultural Science, Southwest University, Chongqing 400715, China.
Int J Mol Sci. 2023 Mar 24;24(7):6125. doi: 10.3390/ijms24076125.
Lipid homeostasis is essential for insect growth and development. The complex of proteins associated with Set 1 (COMPASS)-catalyzed Histone 3 lysine 4 trimethylation (H3K4me3) epigenetically activates gene transcription and is involved in various biological processes, but the role and molecular mechanism of H3K4me3 modification in lipid homeostasis remains largely unknown. In the present study, we showed in that fat body-specific knockdown of () as one of the COMPASS complex components caused a decrease in lipid droplet (LD) size and triglyceride (TG) levels. Mechanistically, Wds-mediated H3K4me3 modification in the fat body targeted several lipogenic genes involved in lipid synthesis and the gene associated with lipid transport to promote their expressions; the transcription factor heat shock factor (Hsf) could interact with Wds to modulate H3K4me3 modification within the promoters of these targets; and fat body-specific knockdown of phenocopied the effects of knockdown on lipid homeostasis in the fat body. Moreover, fat body-specific knockdown of or reduced high-fat diet (HFD)-induced oversized LDs and high TG levels. Altogether, our study reveals that Wds-mediated H3K4me3 modification is required for lipid homeostasis during development and provides novel insights into the epigenetic regulation of insect lipid metabolism.
脂质动态平衡对于昆虫的生长和发育至关重要。与 Set1(COMPASS)催化的组蛋白 3 赖氨酸 4 三甲基化(H3K4me3)相关的蛋白复合物通过表观遗传激活基因转录,参与各种生物学过程,但 H3K4me3 修饰在脂质动态平衡中的作用和分子机制在很大程度上仍然未知。在本研究中,我们表明,脂肪体特异性敲低 COMPASS 复合物的一个组成部分()导致脂滴(LD)大小和三酰甘油(TG)水平降低。在机制上,Wds 在脂肪体中介导的 H3K4me3 修饰靶向了几个参与脂质合成的生脂基因和与脂质转运相关的基因,以促进它们的表达;热休克因子(Hsf)转录因子可以与 Wds 相互作用,调节这些靶基因启动子内的 H3K4me3 修饰;脂肪体特异性敲低导致与脂肪体中脂质动态平衡相关的表型类似于敲低的表型。此外,脂肪体特异性敲低或降低了高脂肪饮食(HFD)诱导的超大 LD 和高 TG 水平。总之,我们的研究揭示了 Wds 介导的 H3K4me3 修饰对于在发育过程中的脂质动态平衡是必需的,并为昆虫脂质代谢的表观遗传调控提供了新的见解。