c-Krox, a transcriptional regulator of type I collagen gene expression, is preferentially expressed in skin.
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.
Galéra
P
P
Department of Molecular Genetics, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Musso
M
M
Ducy
P
P
Karsenty
G
G
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001842:Bone and Bones / Q000378:metabolism; D002460:Cell Line; D003094:Collagen / Q000096:biosynthesis*; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000378:metabolism; D004330:Drosophila; D015870:Gene Expression; D005786:Gene Expression Regulation; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D011401:Promoter Regions, Genetic; D017386:Sequence Homology, Amino Acid; D012867:Skin / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis* / Q000378:metabolism; D014162:Transfection; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D014157:Transcription Factors; C089581:Zfp67 protein, mouse; D003094:Collagen