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PMID: 8474441 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Characterization of cytokine LD78 gene promoters: positive and negative transcriptional factors bind to a negative regulatory element common to LD78, interleukin-3, and granulocyte-macrophage colony-stimulating factor gene promoters.

Molecular and cellular biology ·Vol. 13 ·No. 5 ·1993-05-00 ·Pages 2787-801

Nomiyama H, Hieshima K, Hirokawa K, Hattori T, Takatsuki K, Miura R

Abstract

Cytokine LD78 is a human counterpart of the mouse macrophage inflammatory protein 1 alpha/hematopoietic stem cell inhibitor. Promoters of the LD78 alpha and LD78 beta genes showed similar inducible activities in two leukemic cell lines, K562 and Jurkat, but the induction mechanisms differed between the two cell lines. Further characterization of the LD78 alpha promoter indicated that multiple positive and negative regulatory elements are present, some of which are differentially required for induction and repression of the promoter activity in different cells. One of the negative regulatory elements, ICK-1, functioned in both cell lines in the absence and presence of stimulation and was shown to be a recognition site for positive and negative transcriptional factors. This ICK-1 element contained a direct repeat, and similar repeats were also found in the negative regulatory elements of hematopoietic growth factor interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) gene promoters. Nuclear extracts from K562 and Jurkat cells formed several protein-DNA complexes with the LD78 alpha ICK-1 element, one of which was also observed with the IL-3 and GM-CSF ICK-1 elements. Results from in vivo and in vitro analyses suggested that the protein forming this complex functions as a negative factor. The binding affinity of this protein, ICK-1A, to the LD78 alpha ICK-1 element was low and was significantly affected by the incubation temperature and the salt concentration in the binding buffer. ICK-1B, another protein bound specifically by the LD78 alpha ICK-1 element, was shown to be a positive factor important for induction of the promoter. These results suggested that ICK-1A plays an important role in balanced expression of LD78, IL-3, and GM-CSF during hematopoietic cell growth and differentiation.

MeSH Terms
Animals Base Sequence Cell Nucleus/metabolism Chemokine CCL3 Chemokine CCL4 Chloramphenicol O-Acetyltransferase/genetics,metabolism Cytokines/genetics DNA Probes Granulocyte-Macrophage Colony-Stimulating Factor/genetics Humans Interleukin-3/genetics Leukemia, Erythroblastic, Acute Leukemia, T-Cell Luciferases/genetics,metabolism Macrophage Inflammatory Proteins Methylation Mice Molecular Sequence Data Monokines/genetics Mutagenesis, Site-Directed Neoplasm Proteins/genetics Oligodeoxyribonucleotides Promoter Regions, Genetic/drug effects Regulatory Sequences, Nucleic Acid Restriction Mapping Sequence Deletion Sequence Homology, Nucleic Acid Tetradecanoylphorbol Acetate/pharmacology Transcription Factors/metabolism Transfection Tumor Cells, Cultured
Chemicals
Chemokine CCL3 Chemokine CCL4 Cytokines DNA Probes Interleukin-3 Macrophage Inflammatory Proteins Monokines Neoplasm Proteins Oligodeoxyribonucleotides Transcription Factors Granulocyte-Macrophage Colony-Stimulating Factor Luciferases Chloramphenicol O-Acetyltransferase Tetradecanoylphorbol Acetate
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Nomiyama H
Department of Biochemistry, Kumamoto University Medical School, Japan.
Hieshima K
Hirokawa K
Hattori T
Takatsuki K
Miura R
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.13.5.2787-2801.1993
Published
1993-05-00
Pages
2787-801
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC359660
Subset
IM
External Links
PubMed source DOI: 10.1128/mcb.13.5.2787-2801.1993 PMC Full Text View journal details
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