Open Accessc-Krox, a transcriptional regulator of type I collagen gene expression, is preferentially expressed in skin.
Author(s) -
Philippe Galéra,
Marco Musso,
Patricia Ducy,
Gérard Karsenty
Publication year - 1994
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.91.20.9372
Subject(s) - biology , regulation of gene expression , gene expression , microbiology and biotechnology , transcription factor , type i collagen , gene , genetics , endocrinology
We have cloned a mouse cDNA that is a member of the Krox gene family and encodes a protein we have named c-Krox. The c-Krox protein contains three zinc fingers of the Cys2His2 type. c-Krox binds specifically to a guanine-rich cis-acting element present twice in the promoter element of the mouse alpha 1(I) collagen gene. Study of c-Krox gene expression shows that c-Krox is markedly enriched in skin, one of the two major sites of type I collagen synthesis, but is absent in bone, the other main type I collagen-producing tissue, indicating that type I collagen gene expression is differentially regulated in skin and bone. DNA transfection experiments in mouse NIH 3T3 fibroblasts, cells that express the c-Krox gene, or in Drosophila S2 cells, which do not express c-Krox, reveal that c-Krox can activate transcription of a reporter gene linked to several copies of its binding site in the alpha 1(I) collagen promoter. Thus, c-Krox is only the second member of the Krox family for which a target gene has been identified. The selective spatial pattern of expression of its mRNA and its transcription activation ability suggest that c-Krox may be an important regulator of type I collagen skin specific expression in physiologic conditions and in fibrotic diseases such as scleroderma.