干扰素调节因子：调节脂肪形成的转录

yuji8

Interferon Regulatory Factors Are Transcriptional Regulators of Adipogenesis

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.

http://www.cellmetabolism.org/co ... IIS1550413107003373

作者单位
1 Division of Endocrinology and Metabolism, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
2 Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
3 Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
4 Institute for Genome Sciences & Policy and Department of Pediatrics, Duke University, Durham, NC 27708, USA

干扰素调节因子（IRT）是脂肪细胞形成过程中的转录因子

我们应用整合实验与计算方法，已经确定了的脂肪细胞形成过程中转录途径。

我们采用高通量及高敏性DNA酶分析法，去寻找特定的结合位点，这些位点定位于脂肪细胞基因附近，并能调控与脂肪细胞分化相关染色质的结构。经高敏性实验筛选出的有改变的基因区域，可用来预测脂肪细胞形成相关因子与的结合位点。其中一项代表性实验显示：这些区域包括了IRF超家族的结合位点，其中有几个位点与细胞分化密切相关。因此，IRF能抑制脂肪细胞分化。并且IRFmRNA 表达的改变可调节脂肪细胞形成。

这项研究提示了IRF在脂肪细胞生物学的重要性。也确定了顺式作用元件及反式作用因子（例如IRF）参与脂肪细胞行成过程，并解释了之前的疑问。