Regulation of the promoter for human immunoglobulin gamma3 germ-line transcription and its interaction with the 3'alpha enhancer
UMass Chan Affiliations
Department of Molecular Genetics and MicrobiologyDocument Type
Journal ArticlePublication Date
2000-04-01Keywords
Antigens, CD40B-Lymphocytes
Base Sequence
CCAAT-Enhancer-Binding Proteins
DNA
DNA-Binding Proteins
Drug Synergism
Enhancer Elements (Genetics)
Genes, Immunoglobulin
Humans
Immunoglobulin Class Switching
Immunoglobulin G
Interleukin-4
Molecular Sequence Data
Mutagenesis, Insertional
NF-kappa B
Nuclear Proteins
Phorbol 12,13-Dibutyrate
Promoter Regions (Genetics)
RNA, Messenger
Response Elements
STAT6 Transcription Factor
Trans-Activation (Genetics)
Trans-Activators
Transcription, Genetic
Tumor Cells, Cultured
Life Sciences
Medicine and Health Sciences
Women's Studies
Metadata
Show full item recordAbstract
The mechanism underlying the differential regulation of switching to human IgG subclasses is still largely unknown. We demonstrate that the region upstream of the initiation sites for gamma3 germ-line (GL) transcripts contains a functional promoter which is synergistically induced by IL-4, antibody to CD40 and phorbol dibutyrate in transient transfection assays in the human DG75 cell line. Linker-scanning mutations identified multiple elements in the 3' half of the evolutionarily conserved sequence that are required for inducibility. Electrophoretic mobility shift assays showed that Stat6 and NF-kappaB p50 / p65 are induced after stimulation, and bind to specific sequence motifs within the promoter. Overexpression of Stat6, NF-kappaB p50 / p65 and C / EBPgamma synergistically induced the GL gamma3 promoter. Insertion of DNA segments from the human 3' IgH regions, which may function as a locus control region for switch recombination, greatly activated the promoter in an orientation-independent manner. Duplication of the enhancer fragments resulted in a further increase of promoter activity. The greater enhancement of the HS1,2 fragment from the 3' alpha1 rather than the alpha2 locus may suggest a mechanistic explanation for the differential expression of various isotypes.Source
Eur J Immunol. 2000 Apr;30(4):1019-29.
DOI
10.1002/(SICI)1521-4141(200004)30:4<1019::AID-IMMU1019>3.0.CO;2-WPermanent Link to this Item
http://hdl.handle.net/20.500.14038/50667PubMed ID
10760789Related Resources
ae974a485f413a2113503eed53cd6c53
10.1002/(SICI)1521-4141(200004)30:4<1019::AID-IMMU1019>3.0.CO;2-W