A transcriptional silencer controls the developmental expression of the CD4 gene.
The appropriate expression of the CD4 glycoprotein is required for T-cell function and development. Here we define the transcriptional control elements in the CD4 locus that convey CD(4+)-specific expression of a marker gene in transgenic mice. Using nuclear run-on experiments, we have determined that the major mechanism for CD4 expression control during development is transcriptional. We have identified a developmental stage- and tissue-specific negative regulatory element in the first intron of the murine CD4 gene that has the characteristics of a transcriptional silencer. The CD4 silencer functions to inhibit marker gene expression at two different stages of T-cell development, as well as in non-T hematopoietic cells, and thus is the critical controlling element responsible for T-cell-specific, as well as developmental- and subclass-specific, expression.
Siu
G
G
Department of Microbiology, Columbia University, College of Physicians and Surgeons, New York, NY 10032.
Wurster
A L
AL
Duncan
D D
DD
Soliman
T M
TM
Hedrick
S M
SM
D000818:Animals; D015704:CD4 Antigens / Q000235:genetics*; D016827:CD8 Antigens / Q000235:genetics; D002478:Cells, Cultured; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation / Q000502:physiology*; D005819:Genetic Markers; D015793:HLA-B7 Antigen / Q000235:genetics; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008957:Models, Genetic; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid / Q000502:physiology*; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology; D014158:Transcription, Genetic / Q000502:physiology
D015704:CD4 Antigens; D016827:CD8 Antigens; D005819:Genetic Markers; D015793:HLA-B7 Antigen