AML-1, PU.1, and Sp3 regulate expression of human bactericidal/permeability-increasing protein

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• 作者：Lennartsson ; Andreas ; Pieters ; Katrien ; Ullmark ; Tove ; Vidovic ; Karina ; Gullberg ; Urban
• 关键词：Transcription ; Promoter ; Gene ; Transcription factor ; Myeloid ; Azurophil granule protein ; Bactericidal/permeability increasing protein
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2003
• 出版时间：November 28, 2003
• 年：2003
• 卷：311
• 期：4
• 页码：853-863
• 全文大小：377 K

文摘

Bactericidal/permeability-increasing protein (BPI) is an antimicrobial protein in neutrophils, stored in azurophil granules. Expression of BPI is absent in neutrophils of newborns and patients with secondary granule deficiency (SGD), possibly contributing to dysfunction of neutrophils. We report two alternative transcription start sites at 52 and 22bp upstream of the translation start. A proximal 222bp promoter conferring expression in myeloid cells was identified, and critical cis-acting sites for myeloid expression were contained within the 159bp upstream of translation start. Within this region, direct binding and transactivation by AML-1, PU.1, and Sp3 were demonstrated, as judged by electrophoretic mobility shift analysis. Moreover, transient transfections of C/EBPα or C/EBP? to HeLa cells resulted in increased promoter activity, indicating a direct or indirect role for C/EBP. In conclusion, we provide evidence for AML-1, PU.1, and Sp3 cooperatively and directly mediating BPI-expression during myeloid differentiation.