Back to Search
Start Over
Differentiation-stimulated Activity Binds an ETS-like, Essential Regulatory Element in the Human Promyelocytic defensin-1Promoter
- Source :
- Journal of Biological Chemistry. 273:8727-8740
- Publication Year :
- 1998
- Publisher :
- Elsevier BV, 1998.
-
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 adjacent TA-rich sequence (-32/-25), in assembly of a myeloid-restricted, basal transcription factor complex. The distal site (-62/-59) interacts in vitro with an unidentified activity, distinct from PU.1, ETS-1, PEA3, and ELK-1 (factors with definite binding site similarities), and is greatly stimulated by phosphorylation during granulocytic differentiation of HL-60 cells. Identification of this protein will be important to resolve the molecular mechanisms controlling temporal, granulocytic restricted gene expression.
- Subjects :
- Transcription, Genetic
Recombinant Fusion Proteins
Molecular Sequence Data
Retinoic acid
HL-60 Cells
Regulatory Sequences, Nucleic Acid
Biology
Transfection
Biochemistry
Defensins
chemistry.chemical_compound
Anti-Infective Agents
Transcription (biology)
Gene expression
Tumor Cells, Cultured
Humans
Amino Acid Sequence
Binding site
Promoter Regions, Genetic
Molecular Biology
Defensin
Transcription factor
Gene
Cell Nucleus
Binding Sites
Leukemia
Base Sequence
General transcription factor
Nuclear Proteins
Blood Proteins
Cell Biology
Molecular biology
chemistry
Mutagenesis, Site-Directed
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 273
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....4d1397257b820bd1c069265dd9a9afc8