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J Biol Chem, Vol. 273, Issue 36, 22861-22864, September 4, 1998

COMMUNICATION
Modular Arrangement of Cartilage- and Neural Tissue-specific cis-Elements in the Mouse alpha 2(XI) Collagen Promoter

Noriyuki TsumakiDagger §, Tomoatsu KimuraDagger , Kazuhiro Tanaka§, James H. Kimuraparallel , Takahiro OchiDagger , and Yoshihiko Yamada§

From the Dagger  Department of Orthopaedic Surgery, Osaka University Medical School, Suita 565-0871, Japan, the § Craniofacial Developmental Biology and Regeneration Branch, NIDR, National Institutes of Health, Bethesda, Maryland 20892, and the parallel  Section of Biochemistry, Bone and Joint Center, Henry Ford Hospital, Detroit, Michigan 48202

Type XI collagen, a heterotrimer specific to cartilage matrix, plays an important role in cartilage morphogenesis. We analyzed various alpha 2(XI) collagen promoter-lacZ reporter gene constructs in transgenic mice to understand tissue-specific transcriptional regulation. The -530 promoter sequence was sufficient to direct reporter gene expression specifically to cartilage. Further deletion to -500 abolished reporter gene expression in cartilage but activated the expression specific to neural tissues such as brain and neural tube. An additional 47-base pair deletion resulted in random tissue expression patterns. A 24-base pair sequence from -530 to -507 of the alpha 2(XI) promoter was able to switch the activity of the heterologous neurofilament light gene promoter from neural tissues to cartilage. These results suggest that the alpha 2(XI) collagen gene is regulated by at least three modular elements: a basal promoter sequence distal to -453, a neural tissue-specific element (-454 to -500), and a cartilage-specific element (-501 to -530), which inhibits expression in neural tissues and induces expression in cartilage.


Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.



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