Nichol Donna, Christian Mark, Steel Jennifer H, White Roger, Parker Malcolm G
Institute of Reproductive and Developmental Biology, Imperial College London, Faculty of Medicine, Du Cane Road, London W12 0NN, United Kingdom.
J Biol Chem. 2006 Oct 27;281(43):32140-7. doi: 10.1074/jbc.M604803200. Epub 2006 Aug 21.
RIP140 is a corepressor for nuclear receptors that regulates energy expenditure in adipose tissue by suppressing the expression of clusters of metabolic genes involved in glucose and lipid metabolism. The gene encoding RIP140/Nrip1 contains only one coding exon but has multiple promoters and 5' non-coding exons that are subject to alternative splicing. In adipocytes we have defined a promoter, referred to as P2, that is preferentially utilized and activated during adipogenesis. Expression studies and chromatin immunoprecipitation experiments indicate that estrogen-related receptor alpha (ERRalpha), the level of which increases during adipogenesis in parallel with RIP140, stimulates transcription from the P2 promoter. Further analysis indicates that ERRalpha is capable of activating RIP140 gene transcription by two mechanisms, directly by binding to an estrogen receptor element/ERR element at -650/-633 and indirectly through Sp1 binding sites in the proximal promoter. Thus, the up-regulation of RIP140 by ERRalpha during adipogenesis may provide an inhibitory feedback mechanism to control the expression of many nuclear receptor target genes.
RIP140是核受体的共抑制因子，通过抑制参与葡萄糖和脂质代谢的代谢基因簇的表达来调节脂肪组织中的能量消耗。编码RIP140/Nrip1的基因仅包含一个编码外显子，但有多个启动子和5'非编码外显子，这些外显子会发生可变剪接。在脂肪细胞中，我们定义了一个启动子，称为P2，它在脂肪生成过程中被优先利用和激活。表达研究和染色质免疫沉淀实验表明，雌激素相关受体α（ERRα）在脂肪生成过程中的水平与RIP140平行升高，它刺激P2启动子的转录。进一步分析表明，ERRα能够通过两种机制激活RIP140基因转录，一种是直接通过与-650/-633处的雌激素受体元件/ERR元件结合，另一种是通过近端启动子中的Sp1结合位点间接激活。因此，ERRα在脂肪生成过程中对RIP140的上调可能提供一种抑制性反馈机制，以控制许多核受体靶基因的表达。
