REGULATION OF GENE EXPRESSION IN PHAGOCYTIC CELLS

Indiana Univ-Purdue Univ At Indianapolis, Indianapolis IN

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Abstract

DESCRIPTION: (Adapted from investigator's abstract) 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.