Organization of the promoter region of the human NF-IL6 gene.
In monocyte/macrophages, the human NF-IL6 gene was activated by LPS or PMA. However, a robust response required stimulation of cells with both LPS and PMA. To examine the molecular basis of this response, we isolated human genomic DNA and determined the nucleotide sequence of a segment (6.4 kb) that included the transcription initiation site of the gene. The unique sequences in the 6.4-kb DNA include several potential transcription factor-binding elements that may explain the molecular basis of the activation of the human NF-IL6 gene by signaling molecules that control the immune and inflammatory responses. Deletion analysis localized an LPS+PMA responsive region downstream position -287, with respect to the transcription initiation site of the NF-IL6 gene. The responsive region includes a potential site for interactions with CREB and a region (-287 to -247) that interacts with SP1 and SP3. In functional assays, the potential CREB site responded to cellular stimulation. The region that interacted with SP1 and SP3 augmented the overall level of activity produced in response to LPS+PMA.
Yang
Yingmei
Y
Department of Chemistry, Purdue University, 1393 Brown Building, West Lafayette, IN 47907-1393, USA.
Pares-Matos
Elsie I
EI
Tesmer
Valerie M
VM
Dai
Changhong
C
Ashworth
Sharon
S
Huai
Jie
J
Bina
Minou
M
D001665:Binding Sites; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000096:biosynthesis / Q000235:genetics*; D002478:Cells, Cultured; D006801:Humans; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D020218:Response Elements; D016329:Sp1 Transcription Factor / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D015854:Up-Regulation
D022782:CCAAT-Enhancer-Binding Protein-beta; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; D013755:Tetradecanoylphorbol Acetate