Premium
Induction by interleukin‐6 of interferon regulatory factor 1 (IRF‐1) gene expression through the palindromic interferon response element pIRE and cell type‐dependent control of IRF‐1 binding to DNA.
Author(s) -
Harroch S.,
Revel M.,
Chebath J.
Publication year - 1994
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1994.tb06463.x
Subject(s) - biology , palindrome , response element , irf1 , microbiology and biotechnology , regulatory sequence , interferon regulatory factors , interferon , dna , gene , regulation of gene expression , gene expression , palindromic sequence , promoter , genetics , transcription factor , genome
The effects of interleukin‐6 (IL‐6) on interferon regulatory factor 1 (IRF‐1) gene expression were studied in B‐hybridoma B9 cells which are growth‐stimulated by IL‐6 and breast carcinoma T47D cells which are growth‐inhibited. IL‐6 induced the production of IRF‐1 mRNA and protein in both cell types, but IRF‐1 binding activity to its target DNA sequence was induced only in T47D cells. With B9 cells, there was no IRF‐1 binding but instead strong constitutive binding of the IRF‐2 repressor, indicating that binding of IRF‐1 to DNA is an important regulatory step. The IRF‐1 gene promoter element, palindromic IFN‐response element (pIRE), was found to respond to IL‐6 with high efficiency as compared with IFN‐gamma or IFN‐beta. On this palindromic TTC…GAA sequence, two protein complexes (pIRE‐a and pIRE‐b) were induced within minutes by IL‐6. pIRE‐b is similar to the main complex induced by IFN‐gamma and contains the Stat91 protein. pIRE‐a predominantly induced by IL‐6 is a slowly migrating complex which does not contain Stat91 and has low affinity for IFN‐gamma activated sequence (GAS)‐type sequences. Comparison of the relative effects of IL‐6 and IFN‐gamma shows that pIRE enhancers are differently regulated than GAS elements. Distinct transcription complexes, forming in ratios dependent on the inducer, help explain how various cytokines sharing effects through Stat91 on related enhancers can produce specific patterns of gene expression. Activation of the pIRE‐a factors defines a novel transcriptional activity of IL‐6 in epithelial and lymphoid cells.