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J. Cell Biol.,
Volume 141, Number 6, June 15, 1998 1291-1300
* Department of Biochemistry, The University of Hong Kong, Hong Kong; and Expression of the type II collagen gene (human COL2A1, mouse Col2a1) heralds the differentiation of chondrocytes. It is also expressed in progenitor
cells of some nonchondrogenic tissues during embryogenesis. DNA sequences in the 5' flanking region and
intron 1 are known to control tissue-specific expression
in vitro, but the regulation of COL2A1 expression in
vivo is not clearly understood. We have tested the regulatory activity of DNA sequences from COL2A1 on the
expression of a lacZ reporter gene in transgenic mice.
We have found that type II collagen characteristic expression of the transgene requires the enhancer activity
of a 309-bp fragment (+2,388 to +2,696) in intron 1 in
conjunction with 6.1-kb 5' sequences. Different regulatory elements were found in the 1.6-kb region (+701 to
+2,387) of intron 1 which only needs 90-bp 5' sequences for tissue-specific expression in different components of the developing cartilaginous skeleton. Distinct positive and negative regulatory elements act
together to control tissue-specific transgene expression
in the developing midbrain neuroepithelium. Positive
elements affecting expression in the midbrain were
found in the region from Embryology Unit, Children's Medical Research
Institute, New South Wales 2145, Australia
90 to 1,500 and from +701
to +2,387, whereas negatively acting elements were detected in the regions from 1,500 to 6,100 and +2,388
to +2,855.
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