The matrix attachment region-binding protein SATB1 interacts with multipleelements within the gp91(phox) promoter and is down-regulated during myeloid differentiation

The gp91(phox) gene encodes a component of the respiratory burst NADPH oxid ase complex and is highly expressed in mature myeloid cells. The transcript ional repressor CCAAT displacement protein binds to at least five sites wit hin the proximal gp91(phox) promoter and represses expression prior to term inal phagocyte differentiation. The DNA binding activity of CCAAT displacem ent protein decreases during terminal phagocyte differentiation, thus permi tting the binding of transcriptional activators and induction of gp91(phox) expression. We report here that the matrix attachment region-binding prote in SATB1 interacts with at least seven sites within the -1542 to +12-base p air gp91(phox) promoter. Four additional binding sites for CCAAT displaceme nt protein were also identified. Furthermore, the most proximal SATB1-bindi ng site within the gp91(phox) promoter binds specifically to the nuclear ma trix fraction in vitro. SATB1 expression is downregulated during terminal m yeloid cell differentiation, coincident with induction of gp91(phox) expres sion. Transient transfection assays demonstrate that a SATB1-binding site d erived from the gp91(phox) promoter represses promoter activity in cells ex pressing SATB1. These findings underscore the importance of transcriptional repression in the regulation of gp91(phox) expression and reveal a candida te myeloid cell target gene for SATB1, a factor previously found to be esse ntial for T cell development.