邻苯二甲酸单乙基己基酯（MEHP）是增塑剂邻苯二甲酸二乙基己基酯的主要代谢产物，MEHP暴露可促进脂肪细胞分化，增加脂质积累，研究发现这可能与MEHP引起的转录因子PPARγ与其靶基因相互作用的改变有关，但机制仍待阐明。本研究从核小体定位可影响转录因子与靶基因结合从而对转录调控起重要作用的新思路出发，拟采用前脂肪细胞系(3T3-L1)，分析MEHP对分化不同时期PPARγ的靶基因启动子区核小体定位模式的影响及其与靶基因转录水平之间的关联，研究MEHP导致的核小体定位改变对PPARγ和靶基因反应元件结合的影响，并测定MEHP暴露后靶基因启动子区核小体定位的主要调节因素，并在发育期暴露MEHP的小鼠模型中进行验证，阐明MEHP对PPARγ的靶基因核小体定位的影响及其在脂肪细胞分化中的作用。本项目的开展有助于揭示MEHP促脂肪细胞分化的机制，并为类似化学物质引起肥胖的机制研究提供新的线索。

Mono (2-ethylhexyl) phthalate (MEHP) is the major metabolite of Di-(2-ethylhexyl) phthalate (DEHP) that is a widely used plasticizer. Exposure to MEHP can promote adipocyte differentiation and induce fat accumulation, which is may be associated with the change in the interaction of transcription factor peroxisome proliferator-activated receptor γ (PPARγ) and its target genes induced by MEHP, but the underlying molecular mechanism remains obscure. Based on the previous studies that nucleosome positioning within the promoter plays an important role in the regulation of transcription through interaction with transcription factors and transcription factors binding sites, the research will investigate the effect of MEHP on nucleosome positioning within the promoters of PPARγ target genes in different stages of adipocyte differentiation, and analyze the relationship between nucleosome positioning and the transcription levels of PPARγ target genes. Some representative PPARγ target genes with different levels of transcription will be selected to study the effect of MEHP on the interaction of PPARγ and the response elements on the specific target genes, and its association between nucleosome positioning will be assessed. The status of the main regulators of nucleosome positioning, including chromatin remodeling complex and histone modification, will be studied. In addition, the study will verify the above results in mice perinatally exposed to MEHP. The research will illustrate the role of nucleosome positioning within the promoters of PPARγ target genes in adipocyte differentiation, and provide new insights for the mechanism of adipocyte differentiation induced by MEHP and other similar environmental chemicals.