Interferon regulatory factors are transcriptional regulators of adipogenesis

被引:117
作者
Eguchi, Jun [1 ]
Yan, Qing-Wu [1 ]
Schones, Dustin E. [2 ]
Karnal, Michael [4 ]
Hsu, Chung-Hsin
Zhang, Michael Q. [2 ,3 ]
Crawford, Gregory E. [5 ,6 ]
Rosen, Evan D. [1 ,3 ,4 ]
机构
[1] Beth Israel Deaconess Med Ctr, Div Endocrinol & Metab, Boston, MA 02215 USA
[2] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA
[3] MIT, Broad Inst, Cambridge, MA 02142 USA
[4] Board Inst Harvard, Cambridge, MA 02142 USA
[5] Duke Univ, Inst Genome Sci & Policy, Durham, NC 27708 USA
[6] Duke Univ, Dept Pediat, Durham, NC 27708 USA
关键词
D O I
10.1016/j.cmet.2007.11.002
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:86 / 94
页数:9
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