title: HSF1 regulates expression of G-CSF through the binding element for NF-IL6/CCAAT enhancer binding protein beta.
abstract: Heat shock factor 1 (HSF1) is the major heat shock transcription factor and plays an essential role in mediating the cellular response to physiological and environmental stress. We found that LPS-induced expression of the granulocyte-colony stimulating factor (G-CSF) gene was upregulated in HSF1 knock-out (HSF1(-/-)) mice using a gene array. In order to determine whether and how HSF1 regulates the induced expression of G-CSF, mRNA, and protein levels of G-CSF were detected by Northern blotting and ELISA, the promoter of G-CSF was analyzed with an online transcription element search system and the transcriptional activity of the G-CSF promoter was analyzed by EMSA and a reporter gene assay. The results showed that transcription and protein secretion of G-CSF induced by LPS are both inhibited by HSF1. Three high affinity binding sites for NF-IL6/CCAAT enhancer binding protein beta, but no heat shock element, were identified in the core promoter of G-CSF. The DNA-binding capability of NF-IL6 to the G-CSF promoter was reinforced by LPS but not influenced by heat shock or HSF1. However, HSF1 was observed to bind to the binding sites of NF-IL6 in the G-CSF promoter. The transcriptional activity of the G-CSF promoter was enhanced by LPS or NF-IL6 and inhibited by HSF1 in a dose dependent manner. We conclude that HSF1 regulates expression of G-CSF through binding to the NF-IL6-binding element.
authors: Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, People's Republic of China.
authors: Lingli
authors: L
authors: Zhang
authors: Mingshi
authors: M
authors: Yang
authors: Qiupeng
authors: Q
authors: Wang
authors: Meidong
authors: M
authors: Liu
authors: Qiujuan
authors: Q
authors: Liang
authors: Huali
authors: H
authors: Zhang
authors: Xianzhong
authors: X
authors: Xiao
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics*; D000076249:Heat Shock Transcription Factors; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; C490017:Hsf1 protein, mouse; D014157:Transcription Factors; D016179:Granulocyte Colony-Stimulating Factor