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Genome-wide Analysis using ChIP to Identify Isoform-specific Gene Targets
Published on: July 7, 2010
XBP-1 increases ERalpha transcriptional activity through regulation of large-scale chromatin unfolding
Yan Fang1, Jinghua Yan, Lihua Ding
1Beijing Institute of Biotechnology, Beijing 100850, People's Republic of China; Anhui Agriculture University, Hefei 230036, People's Republic of China.
Abstract:
Human X box binding protein 1 (XBP-1) is a transcription factor essential for hepatocyte growth, the differentiation of plasma cells, and the unfolded protein response. Recently, we have demonstrated that two forms of XBP-1, XBP-1S, and XBP-1U, enhance estrogen receptor alpha (ERalpha)-dependent transcriptional activity in a ligand-independent manner. However, how XBP-1S and XBP-1U regulate ERalpha transcriptional activity remains unknown. Here, we report that XBP-1S and XBP-1U induce large-scale chromatin unfolding by targeting the XBP-1 proteins to an amplified, lac operator-containing chromosome region in mammalian cells. This unfolding activity maps to the transactivation domains of XBP-1S and XBP-1U. Wild-type XBP-1S and XBP-1U, but not the mutants that completely abolished the ERalpha transcriptional activation, increased the chromatin unfolding activity of ERalpha. These data identify a novel function of XBP-1 and suggest that regulation of large-scale chromatin unfolding by XBP-1 may be responsible for the enhancement of ERalpha transcriptional activity.
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