Differentiation-stimulated activity binds an ETS-like, essential regulatory element in the human promyelocytic defensin-1 promoter.

The Journal of Biological Chemistry
Y MaP Tempst

Abstract

The human HNP-defensin-1 gene encodes a peptide antibiotic found exclusively in neutrophils and is key to elimination of microbes. Expression is a marker for the granulocytic lineage and for certain stages of differentiation and is not known to be inducible in mature cells under physiological conditions. Low level of transcription also occurs in HL-60 promyelocytic leukemia cells and is greatly activated upon drug-induced granulocytic maturation and by low doses of retinoic acid, in a strictly cell-specific manner (Herwig, S., Su, Q., Ma, Y., and Tempst, P. (1996) Blood 87, 350-364). We have analyzed a 10-kilobase pair region, upstream of the defensin-1 cap site, for the presence of control elements, and we describe a minimal promoter (position -83 to +82) required to drive transcription in HL-60 cells in a quasi cell-specific manner. Our data also suggest the presence of negative regulatory elements in the -416/-191 region that may further contribute to cell specificity in a chromosomal context. The basal promoter contains two functionally essential, ETS-like (GGAA core sequence) elements. The proximal site (-22/-19) constitutively binds the PU.1 transcription factor in vitro and could function, together perhaps with an adjace...Continue Reading

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Sep 27, 2000·Biochimica Et Biophysica Acta·S Y KwonB J Lee
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