INDUCIBLE AND CELL-TYPE-SPECIFIC EXPRESSION OF VL30 U3 SUBGROUPS CORRELATE WITH THEIR ENHANCER DESIGN

The murine VL30 elements constitute one family of retrotransposons represented in 100 to 200 copies that are dispersed among the mouse chromosomes. On the basis of sequence homology, we have subdivided mouse VL30 members into four distinct U3 subgroups. The use of subgroup-specific probes in Northern (RNA) blot analyses shows that individual VL30 U3 subgroups are expressed in a tissue-specific manner. We show by in situ hybridization of mouse skin treated with 12-O-tetradecanoylphorbol-13-acetate (TPA) that VL30 expression is induced in epidermal keratinocytes but not in dermal fibroblasts. Transient transfections of reporter gene plasmids together with in vitro binding analysis indicate that TPA-induced VL30 transcription specific for keratinocytes is mediated by two cooperating sequence motifs in juxtaposed position. One sequence motif is shown to constitutively bind CREB- and Jun-related proteins in both keratinocytes and fibroblasts, whereas the other is a target for TPA-induced c-Rel/p65(NF-kappa B)-binding activity specifically in keratinocytes. These binding sites are found to be conserved within U3 subgroups and individual U3 regions showing induced expression in TPA-treated mouse epidermis. These results together with a sequence comparison between different U3 subgroups indicate that cell type-specific activity of transcription factors known to regulate VL30 transcription and the presence or absence of their cognate binding sites within individual U3 regions determine inducible and cell type-specific VL30 expression. The variable VL30 U3 regions might thus be useful tools to study inducible and cell type-specific transcription in many different cell systems.