ARRANGEMENT OF A CLUSTER OF 3 MOUSE TYPE-I KERATIN GENES EXPRESSED SEQUENTIALLY DURING ESOPHAGEAL-TYPE EPITHELIAL-CELL DIFFERENTIATION

Keratins are intermediate filament proteins expressed in epithelial ce lls. They are divided into two groups, type I and type II, that must a ssociate to form filaments. The genes encoding these proteins are clus tered in two type-specific loci. In stratified epithelia, differentiat ion of the basal cells is accompanied by a switch in the expression of keratin genes. However, how this switch is controlled is not yet unde rstood. We report here the cloning and mapping of a 55-kb region surro unding the keratin 19 (K19) gene in the mouse genome, This gene encode s a type I subunit expressed in simple and complex epithelia, notably in nonkeratinizing stratified epithelia of internal organs. In these t issues, it is expressed in basal cells and not in suprabasal cells, wh ere the main type I subunit is keratin 13, Using probes corresponding to highly conserved sequences in intermediate filament proteins, we ma pped 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 sam e transcriptional orientation, Because the three genes are expressed t ogether in stratified epithelia and because their order of expression during differentiation is the same as their order on the chromosome, w e suggest that there is a relationship between their genomic organizat ion and the control of their expression. (C) 1994 Academic Press, Inc.