This is a proposal to study the regulation of the myeloid specific gp91-phox gene, which is induced during terminal myeloid differentiation, coincident with the transition of a proliferation progenitor cell to a terminally differentiated phagocyte. The proposal centers around 3 specific aims.
The first aim focuses on determining the role each cis-element and cognate DNA binding protein plays in the myeloid specific induction of gp91-phox expression in response to specific stimuli.
Specific Aim 2 includes efforts to obtain cDNA clones of novel transcription factors that bind tot the gp91-phox promoter. DNA binding factors will be cloned by ligand screening of expression libraries using DNA binding site probes, or by DNA affinity chromatography.
Specific Aim 3 focuses on the study of a putative cDNA clone of HAF-1, a novel DNA binding protein whose binding site in the gp91-phox promoter is mutated in chronic granulomatous disease patients.
| Hawkins, S M; Kohwi-Shigematsu, T; Skalnik, D G (2001) The matrix attachment region-binding protein SATB1 interacts with multiple elements within the gp91phox promoter and is down-regulated during myeloid differentiation. J Biol Chem 276:44472-80 |
