Arrangement of a cluster of three mouse type I keratin genes expressed sequentially during esophageal-type epithelial cell differentiation.

Keratins are intermediate filament proteins expressed in epithelial cells. They are divided into two groups, type I and type II, that must associate to form filaments. The genes encoding these proteins are clustered in two type-specific loci. In stratified epithelia, differentiation of the basal cells is accompanied by a switch in the expression of keratin genes. However, how this switch is controlled is not yet understood. We report here the cloning and mapping of a 55-kb region surrounding the keratin 19 (K19) gene in the mouse genome. This gene encodes a type I subunit expressed in simple and complex epithelia, notably in nonkeratinizing stratified epithelia of internal organs. In these tissues, it is expressed in basal cells and not in suprabasal cells, where the main type I subunit is keratin 13. Using probes corresponding to highly conserved sequences in intermediate filament proteins, we mapped two other genes downstream from the K19 gene. Restriction mapping and sequencing data indicate that they encode the mouse K15 and K13. The three genes are separated by about 5-6 kb, and they are in the same transcriptional orientation. Because the three genes are expressed together in stratified epithelia and because their order of expression during differentiation is the same as their order on the chromosome, we suggest that there is a relationship between their genomic organization and the control of their expression.