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.

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.

Manzella L ，Gualdi R ，Perrotti D ，Nicolaides NC ，Girlando G ，Giuffrida MA ，Messina A ，Calabretta B ... -  《EXPERIMENTAL CELL RESEARCH》

Interferon-gamma regulation of the human mimecan promoter.

Tasheva ES ，Conrad GW 《MOLECULAR VISION》

Negative modulation of alpha1(I) procollagen gene expression in human skin fibroblasts: transcriptional inhibition by interferon-gamma.

Yuan W ，Yufit T ，Li L ，Mori Y ，Chen SJ ，Varga J ... -  《JOURNAL OF CELLULAR PHYSIOLOGY》

Transcription factor IRF-2 exerts its oncogenic phenotype through the DNA binding/transcription repression domain.

Nguyen H ，Mustafa A ，Hiscott J ，Lin R ... -  《ONCOGENE》

Conserved high-affinity NF-kappa B binding site in the interferon regulatory factor-1 promoter is not occupied by NF-kappa B in vivo and is transcriptionally inactive.

Rein T ，Schreck R ，Willenbrink W ，Neubert WJ ，Zorbas H ，Bäuerle PA ... -  《-》