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Molecular and Cellular Biology, November 1998, p. 6641-6652, Vol. 18, No. 11
Muscle Development Unit, Children's Medical
Research Institute, Wentworthville, New South Wales 2145, Australia,1 and
Department of Biological
Chemistry, University of Maryland School of Medicine, Baltimore,
Maryland 212012
Received 21 May 1998/Returned for modification 17 July
1998/Accepted 3 August 1998
The molecular mechanisms which are responsible for restricting
skeletal muscle gene expression to specific fiber types, either slow or
fast twitch, are unknown. As a first step toward defining the
components which direct slow-fiber-specific gene expression, we
identified the sequence elements of the human troponin I slow upstream
enhancer (USE) that bind muscle nuclear proteins. These include an
E-box, a MEF2 element, and two other elements, USE B1 and USE C1. In
vivo analysis of a mutation that disrupts USE B1 binding activity
suggested that the USE B1 element is essential for high-level
expression in slow-twitch muscles. This mutation does not, however,
abolish slow-fiber specificity. A similar analysis indicated that the
USE C1 element may play only a minor role. We report the cloning of a
novel human USE B1 binding protein, MusTRD1 (muscle TFII-I repeat
domain-containing protein 1), which is expressed predominantly in
skeletal muscle. Significantly, MusTRD1 contains two repeat domains
which show remarkable homology to the six repeat domains of the
recently cloned transcription factor TFII-I. Furthermore, both TFII-I
and MusTRD1 bind to similar but distinct sequences, which happen to
conform with the initiator (Inr) consensus sequence. Given the roles of
MEF2 and basic helix-loop-helix (bHLH) proteins in muscle gene
expression, the similarity of TFII-I and MusTRD1 is intriguing, as
TFII-I is believed to coordinate the interaction of MADS-box proteins,
bHLH proteins, and the general transcription machinery.
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Identification of a Novel Slow-Muscle-Fiber
Enhancer Binding Protein, MusTRD1
*
Corresponding author. Mailing address: Muscle
Development Unit, Children's Medical Research Institute, Locked Bag
23, Wentworthville, New South Wales 2145, Australia. Phone:
61-2-9687-2800. Fax: 61-2-9687-2120. E-mail:
ehardeman{at}cmri.usyd.edu.au.
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