Eguchi Jun, Yan Qing-Wu, Schones Dustin E, Kamal Michael, Hsu Chung-Hsin, Zhang Michael Q, Crawford Gregory E, Rosen Evan D
Division of Endocrinology and Metabolism, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Cell Metab. 2008 Jan;7(1):86-94. doi: 10.1016/j.cmet.2007.11.002.
We have sought to identify transcriptional pathways in adipogenesis using an integrated experimental and computational approach. Here, we employ high-throughput DNase hypersensitivity analysis to find regions of altered chromatin structure surrounding key adipocyte genes. Regions that display differentiation-dependent changes in hypersensitivity were used to predict binding sites for proteins involved in adipogenesis. A high-scoring example was a binding motif for interferon regulatory factor (IRF) family members. Expression of all nine mammalian IRF mRNAs is regulated during adipogenesis, and several bind to the identified motifs in a differentiation-dependent manner. Furthermore, several IRF proteins repress differentiation. This analysis suggests an important role for IRF proteins in adipocyte biology and demonstrates the utility of this approach in identifying cis- and trans-acting factors not previously suspected to participate in adipogenesis.
我们试图采用综合实验和计算方法来确定脂肪生成中的转录途径。在此，我们运用高通量DNase超敏分析来寻找关键脂肪细胞基因周围染色质结构改变的区域。显示超敏反应中依赖分化变化的区域被用于预测参与脂肪生成的蛋白质的结合位点。一个高分示例是干扰素调节因子（IRF）家族成员的结合基序。在脂肪生成过程中，所有九种哺乳动物IRF mRNA的表达均受到调控，并且有几种以依赖分化的方式与鉴定出的基序结合。此外，几种IRF蛋白会抑制分化。该分析表明IRF蛋白在脂肪细胞生物学中具有重要作用，并证明了这种方法在鉴定先前未怀疑参与脂肪生成的顺式和反式作用因子方面的实用性。
