Telokin expression in a10 smooth muscle cells requires serum
response factor.
Herring, B. Paul, and Aiping Fan Smith.
Department of Physiology and Biophysics, Indiana University School
of Medicine, 635 Barnhill Drive, Indianapolis, IN 46202-5120
APStracts 3:0377C, 1996.
Telokin transcription is initiated from a smooth muscle-specific
promoter located in an intron of the smooth muscle myosin light chain
kinase gene. Previously we have identified a 310 base pair fragment
of the promoter that mediates A10 smooth muscle cell-specific
expression of telokin. In the current study, telokin-luciferase
reporter gene assays in A10 cells and REF52 nonmuscle cells revealed
that the promoter region between -81 and &80 contains the
regulatory elements required to mediate the in vitro cell-specificity
of the promoter. Several positive acting elements including, an E
box, MEF2/TATA box and CArG/SRE element were identified within this
region. Telokin transcription in A10 smooth muscle cells requires all
three transcription initiation sites and an AT-rich sequence between
-71 and -62 that includes a TATA box. MEF2 interacts with the AT-rich
region with low affinity, however, MEF2 binding is not required for
transcriptional activity in A10 cells. Binding of serum response
factor to a CArG element proximal to the TATA sequence is also
critical for high levels of transcription in A10 cells. Together
these data suggest that an AT-rich motif acting in concert with SRF
and an unusual transcription initiation mechanism are required for
the cell-specific expression of the telokin promoter in A10 smooth
muscle cells.
Received 20 August 1996; accepted in final form 4 November 1996.
APS Manuscript Number C483-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996