Document Detail

The interferon regulatory factors 1 and 2 bind to a segment of the human c-myb first intron: possible role in the regulation of c-myb expression.
MedLine Citation:
PMID:  10739671     Owner:  NLM     Status:  MEDLINE    
The preferential expression of the protooncogene c-myb in hematopoietic cells is in part regulated by a mechanism of transcriptional block in the first intron. By electrophoresis mobility shift assays using probes corresponding to different segments of the putative human c-myb intron 1 transcription pause region and nuclear extracts from myeloid leukemia HL 60 and fibroblast WI 38 cells, we detected a HL-60-specific DNA-protein complex with a 123-bp fragment containing binding sites for the interferon regulatory factors (IRFs) nuclear proteins. Formation of the DNA-protein complex was abrogated by competition with an oligomer containing the wild-type, but not the mutated, IRF binding site and the complex was specifically supershifted by the anti-IRF-1 or the anti-IRF-2 antibody. Moreover, in vitro translated IRF-1 or IRF-2 protein did interact with the 123-bp c-myb intron 1 fragment. Upon TPA-induced differentiation, c-myb expression was readily down-modulated in parental HL 60 cells, but not in cells transfected with an antisense IRF-1 plasmid. Moreover, chloramphenicol acetyltransferase activity driven by a c-myb promoter containing the entire intron 1 was suppressed upon IRF-1, but not IRF-2 expression. Together, these results are consistent with the existence of a functional relationship between IRF-1 and c-myb in which IRF-1 negatively regulates c-myb expression at the transcriptional level by a mechanism that may depend on the interaction of IRF-1 with a segment of the c-myb gene implicated in transcription pausing.
L Manzella; R Gualdi; D Perrotti; N C Nicolaides; G Girlando; M A Giuffrida; A Messina; B Calabretta
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Experimental cell research     Volume:  256     ISSN:  0014-4827     ISO Abbreviation:  Exp. Cell Res.     Publication Date:  2000 Apr 
Date Detail:
Created Date:  2000-05-12     Completed Date:  2000-05-12     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0373226     Medline TA:  Exp Cell Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  248-56     Citation Subset:  IM    
Copyright Information:
Copyright 2000 Academic Press.
Department of Microbiology and Immunology and Kimmel Cancer Institute, Thomas Jefferson University, Bluemle Life Sciences Building, 233 South 10th Street, Philadelphia, Pennsylvania 19107, USA.
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MeSH Terms
Base Sequence
Binding Sites
Chloramphenicol O-Acetyltransferase / genetics
DNA-Binding Proteins / genetics,  metabolism*
Gene Expression Regulation / drug effects
Genes, myb*
Genomic Library
HL-60 Cells
Interferon Regulatory Factor-1
Interferon Regulatory Factor-2
Nuclear Proteins / metabolism
Phosphoproteins / genetics,  metabolism*
Proto-Oncogene Proteins c-myb / genetics
Recombinant Proteins / metabolism
Repressor Proteins*
Tetradecanoylphorbol Acetate / pharmacology
Transcription Factors / metabolism*
Grant Support
Reg. No./Substance:
0/DNA-Binding Proteins; 0/IRF1 protein, human; 0/IRF2 protein, human; 0/Interferon Regulatory Factor-1; 0/Interferon Regulatory Factor-2; 0/Irf1 protein, mouse; 0/Irf2 protein, mouse; 0/Nuclear Proteins; 0/Phosphoproteins; 0/Proto-Oncogene Proteins c-myb; 0/Recombinant Proteins; 0/Repressor Proteins; 0/Transcription Factors; 16561-29-8/Tetradecanoylphorbol Acetate; EC O-Acetyltransferase

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