HSF1 regulates expression of G-CSF through the binding element for NF-IL6/CCAAT enhancer binding protein beta

• Published in: Molecular and cellular biochemistry 2011-06, Vol.352 (1-2), p.11-17
• Main Authors: Zhang, Lingli, Yang, Mingshi, Wang, Qiupeng, Liu, Meidong, Liang, Qiujuan, Zhang, Huali, Xiao, Xianzhong
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Binding sites; Biochemistry; Biomedical and Life Sciences; Blotting, Northern; Blotting, Western; Cardiology; CCAAT-Enhancer-Binding Protein-beta - metabolism; Cell Line; Chemical properties; Cytokines; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; DNA-Binding Proteins - physiology; Electrophoretic Mobility Shift Assay; Environmental stress; Enzyme-Linked Immunosorbent Assay; Gene expression; Genetic research; Genetic transcription; Granulocyte Colony-Stimulating Factor - genetics; Heat shock proteins; Heat Shock Transcription Factors; Life Sciences; Medical Biochemistry; Mice; Mice, Inbred BALB C; Mice, Knockout; Oncology; Promoter Regions, Genetic; Promoters (Genetics); Protein Binding; RNA; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription Factors - physiology
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-010-0624-1

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.