Identification of a novel GC-rich binding protein that binds to an indispensable element for constitutive IRF-4 promoter activity in B cells.
Interferon regulatory factor-4 (IRF-4) is a lymphoid-specific transcription factor that plays crucial roles in the development and the functions of immune cells. B lymphocytes express IRF-4 constitutively. In this report, we investigated the transcriptional control of IRF-4 in B lymphocytes. Successive deletions of the IRF-4 promoter from -4799 revealed that the region between -51 and -28 (5'-CGCCCGCCCCAGGCCCCGCCCCA-3') was required for the basal promoter activity. Mutations in the distal and proximal sites of this GC-rich sequence resulted in 62 and 81% reductions in the IRF-4 promoter activity, respectively. EMSA observations revealed the formation of a protein complex with the corresponding DNA, which was sensitive to mutations in the GC-rich sequences. UV photocrosslinking assays identified a novel 60 kDa protein with a similar sequence preference. The possible involvement of this factor in the regulation of IRF-4 gene expression is discussed.
Nishiya
Naoki
N
Department of Molecular Microbiology and Immunology, Division of Cytokine Signaling, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
Yamamoto
Kazuo
K
Imaizumi
Yoshitaka
Y
Kohno
Tomoko
T
Matsuyama
Toshifumi
T
D001402:B-Lymphocytes / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D020862:GC Rich Sequence / Q000235:genetics / Q000502:physiology; D006801:Humans; D050835:Interferon Regulatory Factors; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D000099218:Interferon Regulatory Factor-4
D004247:DNA; D004268:DNA-Binding Proteins; D050835:Interferon Regulatory Factors; D014157:Transcription Factors; D000099218:Interferon Regulatory Factor-4