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(Received for publication, April 2, 1996, and in revised form, April 19, 1996)
From the Department of Biochemistry, Medical College of Wisconsin,
Milwaukee, Wisconsin 53226
The serum response factor (SRF) is a ubiquitous
transcription factor that plays a central role in the transcriptional
response of mammalian cells to a variety of extracellular signals.
Notably, SRF has been found to be a key regulator of members of a class
of cellular response genes termed immediate-early genes (IEGs), many of
which are believed to be involved in regulating cell growth and
differentiation. The mechanism by which SRF activates transcription of
IEGs in response to mitogenic agents has been extensively studied.
Significantly less is known about how expression of the SRF gene itself
is mediated. We and others have previously shown that the SRF gene is
itself transiently induced by a variety of mitogenic agents and belongs
to a class of ``delayed'' early response genes. We have cloned the
SRF promoter and in the present study have analyzed the upstream
regulatory sequences involved in mediating serum responsiveness of the
SRF gene. Our analysis indicates that inducible SRF expression requires
both SRF binding sites located within the first 63 nucleotides upstream
from the start site of transcriptional initiation and an Sp1 site
located 83 nucleotides upstream from the start site. Maximal
transcriptional activity of the promoter also requires two CCAATT box
sites located 90 and 123 nucleotides upstream of the start site.
Volume 271, Number 28,
Issue of July 12, 1996
pp. 16535-16543
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
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