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.
Eguchi
Jun
J
Division of Endocrinology and Metabolism, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Yan
Qing-Wu
QW
Schones
Dustin E
DE
Kamal
Michael
M
Hsu
Chung-Hsin
CH
Zhang
Michael Q
MQ
Crawford
Gregory E
GE
Rosen
Evan D
ED
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D050156:Adipogenesis / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D047369:Chromatin Immunoprecipitation; D003851:Deoxyribonucleases / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D016133:Polymerase Chain Reaction / Q000379:methods; D011485:Protein Binding; D014158:Transcription, Genetic
D050835:Interferon Regulatory Factors; D003851:Deoxyribonucleases