Histone H3K4me3 modification is a transgenerational epigenetic signal for lipid metabolism in Caenorhabditis elegans.
Qin-Li WanXiao MengChongyang WangWenyu DaiZhenhuan LuoZhinan YinZhenyu JuXiaodie FuJing YangQunshan YeZhan-Hui ZhangQinghua ZhouPublished in: Nature communications (2022)
As a major risk factor to human health, obesity presents a massive burden to people and society. Interestingly, the obese status of parents can cause progeny's lipid accumulation through epigenetic inheritance in multiple species. To date, many questions remain as to how lipid accumulation leads to signals that are transmitted across generations. In this study, we establish a nematode model of C. elegans raised on a high-fat diet (HFD) that leads to measurable lipid accumulation, which can transmit the lipid accumulation signal to their multigenerational progeny. Using this model, we find that transcription factors DAF-16/FOXO and SBP-1/SREBP, nuclear receptors NHR-49 and NHR-80, and delta-9 desaturases (fat-5, fat-6, and fat-7) are required for transgenerational lipid accumulation. Additionally, histone H3K4 trimethylation (H3K4me3) marks lipid metabolism genes and increases their transcription response to multigenerational obesogenic effects. In summary, this study establishes an interaction between a network of lipid metabolic genes and chromatin modifications, which work together to achieve transgenerational epigenetic inheritance of obesogenic effects.
Keyphrases
- high fat diet
- adipose tissue
- dna methylation
- transcription factor
- insulin resistance
- genome wide
- gene expression
- human health
- fatty acid
- metabolic syndrome
- risk assessment
- risk factors
- type diabetes
- weight loss
- signaling pathway
- genome wide identification
- dna damage
- body mass index
- skeletal muscle
- oxidative stress
- high fat diet induced