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Departments of 1 Physiology and Biophysics and of 2 Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, Indiana 46202-5120; and 3 Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas 75235
A cell-specific
promoter located in an intron of the smooth muscle myosin light chain
kinase gene directs transcription of telokin exclusively in smooth
muscle cells. Transgenic mice were generated in which a 310-bp rabbit
telokin promoter fragment, extending from 
163 to +147, was used
to drive expression of simian virus 40 large T antigen. Smooth
muscle-specific expression of the T-antigen transgene paralleled that
of the endogenous telokin gene in all smooth muscle tissues except
uterus. The 310-bp promoter fragment resulted in very low levels of
transgene expression in uterus; in contrast, a transgene driven by a
2.4-kb fragment (2250 to +147) resulted in high levels of
transgene expression in uterine smooth muscle. Telokin expression
levels correlate with the estrogen status of human myometrial tissues,
suggesting that deletion of an estrogen response element (ERE) may
account for the low levels of transgene expression driven by the 310-bp
rabbit telokin promoter in uterine smooth muscle. Experiments in A10
smooth muscle cells directly showed that reporter gene expression
driven by the 2.4-kb, but not 310-bp, promoter fragment could be
stimulated two- to threefold by estrogen. This stimulation was mediated
through an ERE located between 1447 and 1474. Addition of
the ERE to the 310-bp fragment restored estrogen responsiveness in A10
cells. These data demonstrate that in addition to a minimal 310-bp
proximal promoter at least one distal
cis-acting regulatory element is required for telokin expression in uterine smooth muscle. The distal
element may include an ERE between 1447 and 1474.
myosin light chain kinase; estrogen response element; uterus
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