IgH intronic enhancer element HE2 (mu B) functions as a cis-activator in choroid plexus cells at the cellular level as well as in transgenic mice.
Immunoglobulin heavy-chain (IgH) gene expression is regulated largely by the IgH gene intronic enhancer (ENHiH), which is composed of multiple protein-binding motifs. These motifs are DNA elements that are important for the regulation of IgH gene transcription. It has been reported that the HE2 (mu B) and mu A motifs within the ENHiH affect B cell-specific gene expression. To examine the function of the HE2 and mu A elements in vivo, we established transgenic mouse lines. A deletion mutant of the human ENHiH that contains the HE2 and mu A motifs, but lacks the motifs corresponding to murine E5, E3, and octamer, functioned not only in B lymphocytes but also in choroid plexus cells, which secrete CSF. As a result, we obtained choroid plexus tumor-bearing transgenic mice and could establish choroid plexus carcinoma cell lines. In addition, using the luciferase assay, we confirmed at the cellular level that the HE2 motif shows a fair degree of enhancer activity in cultured choroid plexus carcinoma cells. These results suggest the existence of a trans-acting factor for the HE2 motif in choroid plexus cells. Actually, in this cultured cell line, the existence of a protein binding to the HE2 motif was demonstrated by a gel retardation assay. Due to the sequence homology between the HE2 motif and the Ets-binding sites, an Ets-related protein is a highly probable candidate for being the binding factor.
Enjoji
M
M
Department of 3rd Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Iwaki
T
T
Nawata
H
H
Watanabe
T
T
D000818:Animals; D001483:Base Sequence; D002831:Choroid Plexus / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D005803:Genes, Immunoglobulin; D006801:Humans; D007438:Introns; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides