Characterization of the 5'-flanking region and regulation of transcription of human BAFF-R gene.
B-cell activating factor (BAFF) is critical for maintaining the development and homeostasis of B cells. Overexpression of BAFF is associated with autoimmune diseases and malignant B lymphoma. BAFF receptor (BAFF-R) was found to be a specific receptor of BAFF. It not only plays a significant role in splenic B-cell maturation but also works as a major mediator in BAFF-dependent costimulatory response in peripheral B and T cells. Previous studies have demonstrated that BAFF-R is related to several diseases; however, the molecular mechanism of BAFF-R genic transcription has not been clearly defined. The aim of this study was to investigate the transcriptional regulation of the BAFF-R gene. This study was designed to clone and characterize the 5'-regulatory region of the human BAFF-R gene and determine the mechanisms involved in its transcriptional regulation. In addition, the effects of interferon (IFN)-gamma and BAY11-7082 (inhibitor of nuclear factor [NF]-kappaB) on the expression and promoter activity of BAFF-R were examined. The results showed that the sequence between -1420 and +261 could be a core promoter region, and -1562 and -1420 bp harbored a transcriptive silencer. IFN-gamma promoted BAFF-R promoter activity and upregulated BAFF-R mRNA expression. BAY11-7082 (inhibitor of NF-kappaB) exhibited an inhibitory effect on BAFF-R promoter activity and downregulated BAFF-R mRNA expression. Our data provided novel evidence to clarify the mechanism of transcriptional regulation of BAFF-R and illustrated that IFN-gamma and NF-kappaB pathway were involved in regulating BAFF-R expression. Thus some BAFF-R-related diseases might be cured by blocking transcriptional regulation of BAFF-R and reducing its expression.
Yuan
Hongxiang
H
Affiliated Hospital of Nantong University, People's Republic of China.
Wang
Yueguo
Y
Wu
Xinhua
X
Wang
Huiming
H
Pu
Jiang
J
Ding
Weifeng
W
Wang
Mei
M
Shen
Xianjuan
X
Cong
Hui
H
Zhang
Lurong
L
Zhang
Mei
M
Ju
Shaoqing
S
D024506:5' Flanking Region / Q000235:genetics*; D000818:Animals; D053264:B-Cell Activating Factor / Q000378:metabolism; D053265:B-Cell Activation Factor Receptor / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003001:Cloning, Molecular; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics; D009570:Nitriles / Q000494:pharmacology; D010957:Plasmids / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013450:Sulfones / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics*
C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D009570:Nitriles; D012333:RNA, Messenger; D013450:Sulfones; C435926:TNFRSF13C protein, human; D007371:Interferon-gamma; D008156:Luciferases