Regulation of immunoglobulin gene transcription by labile repressor factor(s).
The cloned human gamma 1 heavy chain gene (HIG1) was scarcely expressed in the stable transformants of a mouse fibroblast line, L cell or a T cell line, EL4, and no gamma 1 heavy chain was produced in these cells. Upon treatment with cycloheximide or other kinds of protein synthesis inhibitors, the transcription of HIG1 gene was induced in L cell transformants as well as in T cell transformants. Transcription rate of bacterial gpt gene, which was derived from the plasmid vector used for transfection of HIG1 gene and located just upstream of HIG1 in the transformants, was also greatly enhanced after cycloheximide treatment. But the expression of several endogenous genes in the L cells tested was not affected by the cycloheximide treatment. Nuclear transcription assay indicated that the appearance of HIG1 gene transcripts after treatment with cycloheximide was mainly due to the induction of the transcription. Deletion of an enhancer element from HIG1 gene lowered the inducing activity of cycloheximide in the L cell transformants, but a low level of HIG1 gene expression was still observed. These results suggested that trans-acting factors similar to those present in B lymphoid cells are also functioning in non-B lymphoid cells but their activity is inhibited by short-lived repressor protein(s). Such repressor protein(s) appear to act on regulatory element(s) of the immunoglobulin heavy chain gene including enhancer region as well as 5' flanking region.
D000818:Animals; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics; D003513:Cycloheximide / Q000494:pharmacology; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation / Q000187:drug effects*; D005803:Genes, Immunoglobulin; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis / Q000235:genetics*; D007739:L Cells / Q000378:metabolism; D051379:Mice; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D012097:Repressor Proteins / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000378:metabolism; D014157:Transcription Factors / Q000494:pharmacology* / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured / Q000378:metabolism
D001426:Bacterial Proteins; D007143:Immunoglobulin Heavy Chains; D011994:Recombinant Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D003513:Cycloheximide