Vol. 274, Issue 5, C1187-C1187, May 1998
EDITORIAL FOCUS
Focus on "A 310-bp minimal promoter mediates smooth muscle
cell-specific expression of telokin"
Sheryl L.
White
Department of Molecular Physiology and Biophysics, College of
Medicine, University of Vermont, Burlington, Vermont
05405-0068
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ARTICLE |
SMOOTH MUSCLE CELLS PROVIDE the necessary contractile
force for powering a wide variety of physiological functions and play a
major role in vascular and lung diseases. We are only now beginning to
understand the complex interactions of transcription factors and
regulatory elements involved in dictating smooth muscle-specific gene
regulation. Studies of genes expressed in smooth muscle, including
actin, SM22
, smooth muscle myosin heavy chain, and telokin, have
supplied some pieces of the regulation puzzle, implicating serum
response factor binding at one or more CC(A/T)6GG (CArG) boxes to be a common theme for the activation of these genes in cultured smooth muscle cells (1-3, 5). However, the
behavior of smooth muscle cells under cultured conditions has always
been problematic, as smooth muscle cells in culture are prone to
phenotypic changes, including the loss of differentiated
characteristics (6).
The study of cell-specific promoters in this ever-shifting population
of cells has been difficult, leading to the use of transgenic animals
for promoter analysis. Several promoters have now been used to generate
transgenic mice that direct expression of a reporter gene specifically
in smooth muscle. Expression of the transgenes, however, does not
always exhibit the pattern of the endogenous gene's expression, as has
been demonstrated for SM22 (4) and as is shown by Smith et al. in
the current article in focus (Ref. 7; see p. C1188 in this issue) for
telokin.
The findings of this study (7) add an important piece to the puzzle of
gene regulation in smooth muscle. Smith et al. demonstrate that a
minimal promoter of 310 bp is sufficient for expression of the
transgene in most visceral smooth muscles, with the exception of
uterus. The authors are further able to demonstrate that a 2.4-kb
transgene is expressed in all visceral smooth muscles, including
uterus. This larger promoter fragment contains an estrogen response
element, which is shown to impart estrogen responsiveness in A10 cells
when added to the 310-bp minimal promoter. This report also includes
interesting information on telokin expression in human uterine smooth
muscle, which lends support to the notion that telokin expression is
hormonally regulated in this tissue.
Of considerable interest is the concept, provoked by this report (7)
along with that regarding the SM22 transgene (4), that different
smooth muscle cells may utilize distinct regulatory elements. Although
the estrogen response element is important for expression in smooth
muscle cells in the uterus, it is not required for expression in
intestinal smooth muscle cells, suggesting that even within the
visceral smooth muscles there exist distinct smooth muscle cell types.
This added level of complexity should be an important consideration for
future studies of smooth muscle-specific transcriptional regulation. It
is becoming increasingly apparent that there are diverse populations of
smooth muscle cells that utilize distinct regulatory schemes. While we
continue to struggle with the question of what factors are necessary
for smooth muscle differentiation, the report by Smith et al. (7)
reveals additional questions that must be answered, such as, What
factors are involved in specifying these distinct smooth muscle cell
lineages?
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REFERENCES |
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Blank, R. S.,
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Herring, B. P.,
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Madsen, C. S.,
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Expression of the smooth muscle myosin heavy chain gene is regulated by a negative-acting GC-rich element located between two positive-acting serum response factor-binding elements.
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Owens, G. K.
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Smith, A. F.,
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A 310-bp minimal promoter mediates smooth muscle cell-specific expression of telokin.
Am. J. Physiol.
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C1188-C1195,
1998[Abstract/Free Full Text].
AJP Cell Physiol 274(5):C1187-C1187
0363-6143/98 $5.00
Copyright © 1998 the American Physiological Society
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