CHARACTERIZATION OF A HAIR (WOOL) KERATIN INTERMEDIATE FILAMENT GENE DOMAIN

In epithelial differentiation keratin intermediate filament genes are expressed in multifarious tissue-specific and stage-specific patterns. Pairs of type I and type II intermediate filament genes, belonging to multigene families, are coordinately regulated, and 4 - 5 genes of ea ch type are expressed in the hair follicle. Accumulating chromosomal m apping data points to a major locus for each intermediate filament mul tigene family on separate chromosomes. In this report we describe the isolation of a sheep hair keratin cosmid and chromosome walking that o verlaps two previously described cosmids and establishes a continuous 100-kb segment of cloned DNA containing three hair and three hair-like type II intermediate filament keratin genes. A new hair keratin type II interme-diate filament gene, KRT2.11, is located in the middle of t he cluster, and partial sequence data reveal a striking conservation o f its predicted N-terminal region with other sheep hair keratin type I I intermediate filament proteins. Expression analyses demonstrate the presence of a 2.4-kb KRT2.11 transcript in wool follicle RNA and show that expression occurs in the follicle cortical keratinocytes above th e dermal papilla. The three hair genes are clustered within about 40 k b and flanked by hair-like genes that are not expressed in the hair fo llicle, thereby demarcating a hair keratin gene domain.