Modulation of the IgH enhancer's cell type specificity through a genetic switch

• Published in: Genes & development Vol. 5; no. 1; pp. 29 - 37
• Main Authors: RUEZINSKY, D, BECKMANN, H, KADESCH, T
• Format: Journal Article
• Language: English
• Published: Cold Spring Harbor, NY Cold Spring Harbor Laboratory 1991
• Subjects: Base Sequence; Basic Helix-Loop-Helix Transcription Factors; Biological and medical sciences; Cells, Cultured; DNA - genetics; Enhancer Elements, Genetic; Fundamental and applied biological sciences. Psychology; Immunoglobulin Heavy Chains - genetics; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Plasmids; Promoter Regions, Genetic; Substrate Specificity; Transcription Factors - genetics; Transcription, Genetic; Transcription. Transcription factor. Splicing. Rna processing; Transfection; In vitro transcription; Immunoglobulins; Rodentia; 3T3-Cell line; Repression; Vertebrata; Regulation(control); Enhancer sequence; Mammalia; Cell line; Type specificity; Transfection; Enzymatic activity; Mouse; Transcription factor; Cell
• ISSN: 0890-9369; 1549-5477
• DOI: 10.1101/gad.5.1.29

Using defined regions of the immunoglobulin heavy-chain enhancer linked to minimal promoters and cDNAs that encode the two helix-loop-helix transcription factors ITF-1 and TFE3, we demonstrate that activity of an otherwise repressed enhancer can be stimulated in nonlymphoid cells. Repression in non-B cells is mediated by the microE5 motif. Derepression occurs at two levels. First, overexpression of ITF-1, and E12/E47-related protein that binds the microE5 motif, leads to transcriptional activation itself. Second, binding of ITF-1 physically displaces a repressor that normally blocks the stimulatory activity of TFE3, which binds the neighboring microE3 motif. TFE3 can only stimulate enhancer activity in the presence of ITF-1 or in the absence of a microE5 motif. Hence, one component of the enhancer's cell type specificity can be artificially modulated through a "genetic switch" in which activity is dictated by the relative levels of ITF-1 and a competing repressor.