Fig. 8. Model of E-cadherin regulation in the cadherin cluster. Parts of the P- and E-cadherin locus are shown. Exons are represented by vertical black bars and numbers, DHSs by vertical arrows, transcription start sites by small horizontal arrows, E-boxes by red boxes and sequences with enhancing activities by green boxes (intron 1-enhancer represented by unlabeled box). alt., sequences that mediate alternative, intron 2-independent gene activation in late embryogenesis; brain, sequences that contribute to brain-specific expression; endoderm, sequences required for endoderm-specific expression; enh., sequences that generally enhance transcription; sil., brain-specific silencer that restricts gene activity to E-cadherin expression domains; tse1-4, tissue-specific enhancers, including elements for ectoderm-specific expression. The presence of a locus control region (LCR) is not yet proven and the precise positions of `sil.', `tse1-4' and `alt.' are unknown. Elements that contribute to expression in yolk sac must be located outside of intron 2. E-boxes are required for downregulation of the gene (red arrow), whereas elements in intron 2 activate the locus (green arrows). The postulated LCR might influence gene activity for proper activation and downregulation (purple arrow).