| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Research Abstract |
The chipmunk hibernation-specific proteins HP-20, HP-25 and HP-27 were identified as components of a 140 kDa complex that decreases drastically in the blood during hibernation. The hibernation-specific genes encoding HP-20, HP-25 and HP-27 are expressed specifically in the liver and are downregulated during hibernation. The liver-specific transcription of the HP-20 and HP-25 genes are activated by HNF-1 and HNF-4, respectively. In this study, we first investigated other transcription factors involved in the liver-specific transcription of the hibernation-specific genes, and to date, revealed that the HP-20, HP-25 and HP-27 genes are activated by HNF-1, HNF-4 and USF, by HNF-4 and USF, and by USF, respectively. Next, to analyze whether these transcription factors are involved in the transcriptional regulation of the HP-20, HP-25 and HP-27 genes in vivo, we performed chromatin immunoprecipitation (ChIP) using anti-HNF-1, anti-HNF-4 and anti-USF antibodies. ChIP revealed that these transcription factors bound to the promoter region of the respective hibernation-specific genes in the liver of nonhibernating chipmunk, indicating that these transcription factors are involved in the transcriptional regulation of the hibernation-specific genes in vivo. ChIP also revealed that the transcription factors bound to the hibernation-specific gene promoters even in the liver of hibernating chipmunks in which their transcription is repressed. We then analyzed whether epigenetic modifications are involved in the hibernation-associated transcriptional regulation. ChIP revealed that histone H3 bound to the promoter regions of the hibernation-specific genes was acetylated at lysine 14 in nonhibernating chipmunks, but not in hibernating chipmunks. Taken together, these results indicate that the hibernation-associated transcription of the chipmunk hibernation-specific genes is regulated mainly by epigenetic modification including histone acetylation.
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