The matrix attachment region-binding protein SATB1 interacts with multiple elements within the gp91phox promoter and is down-regulated during myeloid differentiation
The matrix attachment region-binding protein SATB1 interacts with multiple elements within the gp91phox promoter and is down-regulated during myeloid differentiation
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DOI：
10.1074/jbc.m104193200
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发表时间：
2001-11-30
影响因子：
4.8
通讯作者：
Skalnik, DG
中科院分区：
文献类型：
--
作者：
Hawkins, SM;Kohwi-Shigematsu, T;Skalnik, DG
Gp91(Phox)基因编码呼吸爆发NADPH氧化酶复合体的一个组成部分，在成熟的髓系细胞中高度表达。转录抑制因子CCAAT置换蛋白与gp91(Phox)启动子近端的至少5个位点结合，并在吞噬细胞终末分化之前抑制表达。在吞噬细胞终末分化过程中，CCAAT置换蛋白的DNA结合活性降低，从而允许转录激活因子的结合并诱导gp91(Phox)的表达。我们在这里报道了基质附着区结合蛋白SATB1与-1542到+12碱基对gp91(Phox)启动子中的至少7个位点相互作用。还鉴定了CCAAT置换蛋白的另外四个结合位点。此外，gp91(Phox)启动子中最近端的SATB1结合位点在体外与核基质组分特异结合。在终末髓系细胞分化过程中，SATB1的表达下调，这与gp91(Phox)的表达诱导相一致。瞬时转染分析表明，在表达SATB1的细胞中，gp91(Phox)启动子的SATB1结合位点抑制了启动子的活性。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的候选髓系细胞靶基因，这是先前发现的对T细胞发育至关重要的因子。
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 downregulated 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.