Differentiation-stimulated activity binds an ETS-like, essential regulatory element in the human promyelocytic defensin-1 promoter Journal Article
| Authors: | Ma, Y.; Su, Q.; Tempst, P. |
| Article Title: | Differentiation-stimulated activity binds an ETS-like, essential regulatory element in the human promyelocytic defensin-1 promoter |
| 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. |
| Keywords: | protein phosphorylation; leukemia; human cell; promoter region; polymerase chain reaction; blood proteins; transcription initiation; transcription factor; cell differentiation; transcription, genetic; tumor cells, cultured; peptide; transfection; cell specificity; nuclear proteins; gene expression regulation; amino acid sequence; molecular sequence data; recombinant fusion proteins; nucleotide sequence; leukemia cell; base sequence; mutagenesis, site-directed; binding sites; cell nucleus; oligonucleotide; retinoic acid; granulocyte; regulatory sequences, nucleic acid; anti-infective agents; promoter regions (genetics); hl-60 cells; cell strain hl 60; defensin; defensins; humans; human; priority journal; article |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 273 |
| Issue: | 15 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 1998-04-10 |
| Start Page: | 8727 |
| End Page: | 8740 |
| Language: | English |
| DOI: | 10.1074/jbc.273.15.8727 |
| PUBMED: | 9535850 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 12 December 2016 -- Source: Scopus |
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