C-KROX BINDS TO SEVERAL SITES IN THE PROMOTER OF BOTH MOUSE TYPE-I COLLAGEN GENES - STRUCTURE FUNCTION STUDY AND DEVELOPMENTAL EXPRESSION ANALYSIS/

We have previously shown that c-Krox is a zinc finger protein that can increases the transcriptional activity of the mouse alpha 1(I) collag en promoter through its binding to two GC-rich sequences (Galera, P,, Musso, Ri,, Ducy, P,, and Karsenty, G, (1994) Proc, Natl, Acad, Sci, U , S. A, 91, 9372-9376), In this report we show that c-Krox can bind to an additional site in the promoter of the alpha 1(I) collagen gene an d to three sites in the promoter of the alpha 2(I) collagen gene, the other gene coding for type I collagen, One of the binding sites presen t in both promoters is adjacent to the CCAAT box, We have performed a structure/function analysis of c-Krox locating the transactivation dom ain in the zinc finger and C-terminal domains and the dimerization dom ain in the C-terminal end of the protein, We also demonstrate that c-K rox is an early response gene, whose expression is detectable as early as 9.5-day postcoitum in mouse embryos, Whole-mount in situ hybridiza tion shows that c-Krox is expressed in dermatomes, the somite derivati ves that generate dermis, and section in situ hybridization shows that c-Krox and alpha 1(I) collagen mRNAs colocalized in skin but not in b one during development, This result is consistent with the predominant expression of c-Krox in skin in postnatal life, Thus, our findings su ggest that c-Krox is one transcription factor controlling the coordina ted expression of the two type I collagen genes in skin.