The matrix attachment region-binding protein SATB1 interacts with multiple elements within the gp91phox promoter and is down-regulated during myeloid differentiation.
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.
Hawkins
S M
SM
Herman B Wells Center for Pediatric Research, Section of Pediatric Hematology/Oncology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
Kohwi-Shigematsu
T
T
Skalnik
D G
DG
D000818:Animals; D001665:Binding Sites; D015153:Blotting, Western; D019556:COS Cells; D002454:Cell Differentiation; D019070:Cell Lineage; D004262:DNA Restriction Enzymes / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000502:physiology*; D015536:Down-Regulation; D005109:Extracellular Matrix / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D036961:Matrix Attachment Region Binding Proteins; D008562:Membrane Glycoproteins / Q000235:genetics*; D008957:Models, Genetic; D023461:Myeloid Progenitor Cells / Q000166:cytology*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D009841:Oligonucleotides / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011993:Recombinant Fusion Proteins; D013601:T-Lymphocytes / Q000378:metabolism; D014162:Transfection
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D036961:Matrix Attachment Region Binding Proteins; D008562:Membrane Glycoproteins; D009841:Oligonucleotides; D011993:Recombinant Fusion Proteins; C076189:SATB1 protein, human; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D004262:DNA Restriction Enzymes