Identification of an orthologous mammalian cytokeratin gene. High degree of intron sequence conservation during evolution of human cytokeratin 10.
Among the human acidic (type I) cytokeratins, components 10 and 11 are especially interesting, as they are under various kinds of expression control. They are synthesized in the suprabasal cell layers of certain stratified epithelia, notably epidermis, in an endogenous differentiation program; they are expressed in certain epithelial tumours but not in others; they can appear de novo in certain pathological situations such as in squamous metaplasias; and their expression in vivo and in vitro is under positive influence of extracellular calcium concentrations and is reduced in the presence of vitamin A or other retinoids. To provide a basis for studies of the various regulatory elements, we have isolated the human gene encoding cytokeratin 10, using a cDNA probe derived from the corresponding bovine gene, and have sequenced the mRNA coding region as well as adjacent regions approximately 1500 bases 5' upstream and 1000 bases 3' downstream. The eight exons encode a polypeptide 59,535 Mr, i.e. somewhat larger than the corresponding bovine and murine proteins. The deduced amino acid sequences display a high degree of homology, which is not restricted to the exons and the 5' and 3' adjacent regions but, surprisingly, is also evident in the seven introns, some of which contain extended sequence elements with 70% identical nucleotides and more, i.e. similar to the homology in the adjacent exons. This exceptionally high level of conservation of intron sequences is discussed in relation to the recently accumulating evidence of the occurrence of intron sequences important in the regulation of the expression of members of other multigene families during development.