IgH Intronic Enhancer Element HE2 (μB) Functions as a cis‐Activator in Choroid Plexus Cells at the Cellular Level as well as in Transgenic Mice

Abstract: Immunoglobulin heavy‐chain (IgH) gene expression is regulated largely by the IgH gene intronic enhancer (ENH_iH), 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 (μB) and μA motifs within the ENH_iH affect B cell‐specific gene expression. To examine the function of the HE2 and μA elements in vivo, we established transgenic mouse lines. A deletion mutant of the human ENH_iH that contains the HE2 and μA 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 that 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.