A CD30 responsive element in the germline epsilon promoter that is distinct from and inhibitory to the CD40 response element.
Germline epsilon (I epsilon) transcription is requisite for IgE switch recombination. I epsilon transcription is markedly increased by ligation of CD40 and/or by IL-4 stimulation. By contrast, we found previously that stimulation through CD30 inhibits I epsilon transcription in EBV-transformed B cell lines. To characterize the molecular mechanisms involved in these contradictory events, the promoter elements that are responsible for I epsilon transcriptional regulation were determined using stable CAT reporter gene constructs. The results define a 95 bp CD30 responsive element (CD30RE) located 5' of the previously defined CD40 responsive element (CD40RE) that resides within the same 95 bp fragment as the IL-4RE and ablates CD40L induced I epsilon promoter activity. However, IL-4 overrides the inhibitory effect of CD30L. These results define a CD30RE and provide further evidence for the complex regulation of I epsilon transcription by various members of the CD40L/TNF alpha family of molecules.
Jumper
M D
MD
Harold C. Simmons Arthritis Research Center, University of Texas Southwestern Medical Center at Dallas 75235-8884, USA.
Fujita
K
K
Lipsky
P E
PE
Meek
K
K
D001483:Base Sequence; D023201:CD40 Ligand; D002461:Cell Line, Transformed; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology* / Q000378:metabolism*; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D017730:Ki-1 Antigen / Q000276:immunology* / Q000378:metabolism*; D008024:Ligands; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000276:immunology* / Q000378:metabolism; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000276:immunology*; D014157:Transcription Factors / Q000276:immunology
D017730:Ki-1 Antigen; D008024:Ligands; D008562:Membrane Glycoproteins; D014157:Transcription Factors; D023201:CD40 Ligand; D015847:Interleukin-4; D007073:Immunoglobulin E