XBP-1 increases ERalpha transcriptional activity through regulation of large-scale chromatin unfolding.
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.
Fang
Yan
Y
Beijing Institute of Biotechnology, Beijing 100850, People's Republic of China; Anhui Agriculture University, Hefei 230036, People's Republic of China.
Yan
Jinghua
J
Ding
Lihua
L
Liu
Yufei
Y
Zhu
Jianhua
J
Huang
Cuifen
C
Zhao
Haiquan
H
Lu
Qiujun
Q
Zhang
Xuemin
X
Yang
Xiao
X
Ye
Qinong
Q
D002454:Cell Differentiation; D002460:Cell Line; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D008024:Ligands; D008156:Luciferases / Q000378:metabolism; D009154:Mutation; D010957:Plasmids / Q000378:metabolism; D011489:Protein Denaturation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D000071717:X-Box Binding Protein 1
D002843:Chromatin; D004268:DNA-Binding Proteins; D047628:Estrogen Receptor alpha; D008024:Ligands; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; D008156:Luciferases