Hawkins S M, Kohwi-Shigematsu T, Skalnik D G
Herman B Wells Center for Pediatric Research, Section of Pediatric Hematology/Oncology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
J Biol Chem. 2001 Nov 30;276(48):44472-80. doi: 10.1074/jbc.M104193200. Epub 2001 Sep 27.
The gp91(phox) gene encodes a component of the respiratory burst NADPH oxidase complex and is highly expressed in mature myeloid cells. The transcriptional repressor CCAAT displacement protein binds to at least five sites within the proximal gp91(phox) promoter and represses expression prior to terminal phagocyte differentiation. The DNA binding activity of CCAAT displacement protein decreases during terminal phagocyte differentiation, thus permitting the binding of transcriptional activators and induction of gp91(phox) expression. We report here that the matrix attachment region-binding protein SATB1 interacts with at least seven sites within the -1542 to +12-base pair gp91(phox) promoter. Four additional binding sites for CCAAT displacement protein were also identified. Furthermore, the most proximal SATB1-binding site within the gp91(phox) promoter binds specifically to the nuclear matrix fraction in vitro. SATB1 expression is down-regulated during terminal myeloid cell differentiation, coincident with induction of gp91(phox) expression. Transient transfection assays demonstrate that a SATB1-binding site derived from the gp91(phox) promoter represses promoter activity in cells expressing SATB1. These findings underscore the importance of transcriptional repression in the regulation of gp91(phox) expression and reveal a candidate myeloid cell target gene for SATB1, a factor previously found to be essential for T cell development.
gp91(phox)基因编码呼吸爆发NADPH氧化酶复合物的一个组分,在成熟髓样细胞中高度表达。转录抑制因子CCAAT位移蛋白与近端gp91(phox)启动子内至少五个位点结合,并在终末吞噬细胞分化之前抑制其表达。在终末吞噬细胞分化过程中,CCAAT位移蛋白的DNA结合活性降低,从而允许转录激活因子结合并诱导gp91(phox)表达。我们在此报告,核基质附着区结合蛋白SATB1与-1542至+12碱基对的gp91(phox)启动子内至少七个位点相互作用。还鉴定出另外四个CCAAT位移蛋白的结合位点。此外,gp91(phox)启动子内最靠近近端的SATB1结合位点在体外特异性结合核基质组分。在终末髓样细胞分化过程中,SATB1表达下调,这与gp91(phox)表达的诱导同时发生。瞬时转染试验表明,源自gp91(phox)启动子的SATB1结合位点在表达SATB1的细胞中抑制启动子活性。这些发现强调了转录抑制在gp91(phox)表达调控中的重要性,并揭示了SATB1的一个候选髓样细胞靶基因,SATB1是先前发现对T细胞发育至关重要的一个因子。