CHARACTERIZATION AND CHROMOSOMAL LOCALIZATION OF HUMAN HAIR-SPECIFIC KERATIN GENES AND COMPARATIVE EXPRESSION DURING THE HAIR-GROWTH CYCLE

During anagen, cell proliferation in the germinative matrix of the hai r follicle gives rise to the fiber and inner root sheath. The hair fib er is constructed from structural proteins belonging to four multigene families: keratin intermediate filaments, high-sulfur matrix proteins , ultra high-sulfur matrix proteins, and high glycine-tyrosine protein s, Several hair-specific keratin intermediate filament proteins have b een characterized, and all have relatively cysteine-rich N- and C-term inal domains, a specialization that allows extensive disulfide cross-l inking to matrix proteins, We have cloned two complete type II hair-sp ecific keratin genes (ghHb1 and ghHb6). Both genes have nine exons and eight introns spanning about 7 kb and lying about 10 kb apart, The st ructure of both genes is highly conserved in the regions that encode t he central rod domain but differs considerably in the C-terminal codin g and noncoding sequences, although some conservation of introns does exist, These genes have been localized to the type II keratin cluster on chromosome 12q13 by fluorescence in situ hybridization, They, and t heir type I partner ghHa1, are expressed in differentiating hair corti cal cells during anagen, In cultured follicles, ghHa1 expression decli ned in cortical cells and was no longer visible after 6 d, whereas the basal epidermal keratin hK14 appeared in the regressing matrix, The t ransition from anagen to telogen is marked by downregulation of hair c ortical specific keratins and the appearance of hK14 in the epithelial sac to which the telogen hair fiber is anchored, Further studies of t he regulation of these genes will improve our understanding of the cyc lical molecular changes that occur as the hair follicle grows, regress es, and rests.