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KMID : 0381120100320040369
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Genes and Genomics
2010 Volume.32 No. 4 p.369 ~ p.374
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The HAT domain of p300 is critical for the basal Ig germ-line α promoter activity while Stat-1 and E1A act as strong repressors
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Park Seok-Rae
Jung Mee-Hyeun
Kim Pyeung-Hyeun
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Abstract
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p300 acts as a coactivator for TGF-β1-induced Ig germ-line (GL) α transcription. To understand the exact role of p300, we analyzed known domains of p300 using several deletion mutants. p300 mutants lacking both the histone acetyltransferase (HAT) and Smad-binding domains did not enhance GLα promoter activity. In addition, Smad-binding domain within p300 was not sufficient for the promoter activity. Surprisingly, overexpression of a p300 mutant retaining the HAT domain but lacking the rest of downstream segment, p300[N1736], greatly augmented the GLα promoter activity, regardless of TGF-β1 treatment, to levels much higher than that of p300[WT]. Together, these results suggest that HAT activity of p300 is required for GLα promoter activity. We found that p300[N1736] binds to the GLα promoter using ChIP assays. Further analysis of p300[N1736] indicated that both Stat1 and HDAC1 can inhibit the enhancing effect of p300[N1736], suggesting the importance of the Stat1-binding domain and the HAT domain. E1A, a repressor of p300[WT], had no effect on the activity of p300[N1736], which also lacks the E1A-binding domain. Finally, when the amount of transfected p300[N1736] was reduced 40-fold, p300[N1736] functioned similarly to overexpressed p300[WT]. Thus, p300 [N1736], though not having a Smad3-binding domain, augmented TGF-β1-induced GLα promoter activity, which was inhibited by IFN-γ/Stat-1. Taken together, these results indicate that p300 acts as a basal element in GLα transcription without binding to Smad3. Additionally, E1A, Stat1, and HDAC1 act as repressors of p300 in such transcription.
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KEYWORD
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p300, Germ-line α transcripts, IgA, TGF-β1, Smad3, FN-γ
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