CD4 regulation in human lymphoid non-T-cells: a role for the silencer element.
In humans, the CD4 molecule is expressed on a subset of T-cells and at various levels on myeloid and lymphoid cells. The mechanisms regulating human CD4 gene expression are yet poorly understood. We speculated that the CD4 silencer, which operates in CD8+ T-cells to repress CD4 expression, could be responsible for CD4 repression in human lymphoid non-T-cells. To test this possibility, we used lentiviral vectors carrying CD4 regulatory sequences, with or without the silencer element, to express an eGFP reporter gene. We observed that (i) in the absence of the silencer element, eGFP expression was detected in CD34+-derived B- and NK-cells that otherwise lacked endogenous CD4 mRNA, indicating active repression of the CD4 regulatory sequences and (ii) the addition of the CD4 silencer could repress eGFP expression in these same cells, as well as in human B-cells generated in vivo in NOD/SCID mice. Collectively, our results suggest that beyond its well-characterized function in T-cells, the CD4 silencer also regulates CD4 gene expression in human lymphoid non-T-cells.
Mouly
Enguerran
E
Université Pierre et Marie Curie/CNRS UMR 7087, Groupe Hospitalier Pitié-Salpêtrière, 83 Boulevard de l'Hôpital, 75651 Paris cedex 13, France.
Dorival
Céline
C
Pflumio
Françoise
F
Baillou
Claude
C
Coulombel
Laure
L
Levy
Yves
Y
Lemoine
François M
FM
Klatzmann
David
D
Marodon
Gilles
G
D015704:CD4 Antigens / Q000235:genetics* / Q000276:immunology; D002460:Cell Line; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation / Q000276:immunology; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D006801:Humans; D008221:Lymphoid Tissue / Q000276:immunology*; D011401:Promoter Regions, Genetic; D037941:Silencer Elements, Transcriptional; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D015704:CD4 Antigens; D049452:Green Fluorescent Proteins