Regulation of the human Fc epsilon RI alpha-chain distal promoter.
The alpha-chain of the high affinity receptor for IgE (Fc epsilon RI) is essential for cell surface expression of Fc epsilon RI and binding of the IgE Ab. The human alpha-chain gene possesses two promoters: the proximal promoter, which is highly conserved with that of rodent; and the distal promoter, the structure and role of which are largely unknown. Transcriptional regulation of the alpha-chain distal promoter was investigated in this study. Transient reporter assay revealed critical region for transcription activity located within -27/-17. EMSA identified Elf-1, YY1, and PU.1 as transcription factors binding to this region. In contrast to the proximal promoter, which was trans-activated by YY1 and PU.1, these transcription factors exhibited repressive function on this promoter. Addition of IL-4 caused a marked increase in transcription from the distal promoter and subsequently increased the intracellular production of the alpha-chain. These results indicate that IL-4-dependent up-regulation of the human alpha-chain was due to enhancement of distal promoter activity and suggests that the two promoters have different regulatory mechanisms for alpha-chain expression.
Hasegawa
Masanari
M
Atopy (Allergy) Research Center, Juntendo University School of Medicine, Tokyo, Japan.
Nishiyama
Chiharu
C
Nishiyama
Makoto
M
Akizawa
Yushiro
Y
Takahashi
Kyoko
K
Ito
Tomonobu
T
Furukawa
Susumu
S
Ra
Chisei
C
Okumura
Ko
K
Ogawa
Hideoki
H
D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000302:isolation & purification / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D050981:Erythroid-Specific DNA-Binding Factors; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology*; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000276:immunology*; D011518:Proto-Oncogene Proteins / Q000302:isolation & purification / Q000378:metabolism; D017455:Receptors, IgE / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D012045:Regulatory Sequences, Nucleic Acid / Q000276:immunology; D012097:Repressor Proteins / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology; D015534:Trans-Activators / Q000302:isolation & purification / Q000378:metabolism; D014157:Transcription Factors / Q000302:isolation & purification / Q000378:metabolism; D024363:Transcription Initiation Site; D014407:Tumor Cells, Cultured; D050986:YY1 Transcription Factor; D000099232:Proto-Oncogene Protein Spi-1
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D015847:Interleukin-4; D011518:Proto-Oncogene Proteins; D017455:Receptors, IgE; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D050986:YY1 Transcription Factor; D000099232:Proto-Oncogene Protein Spi-1; C494698:YY1 protein, human