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(Received for publication, November 18, 1994; and in revised form, December 13, 1994) MRF4 is a member of the basic helix-loop-helix (bHLH) family of
muscle-specific transcription factors, which also includes MyoD,
myogenin, and myf5. The myocyte enhancer binding factor 2 (MEF2)
proteins also serve as important muscle-specific transcription factors.
In addition to activating the expression of many muscle-specific
structural genes, various members of these two classes of proteins
activate their own expression and the expression of each other in a
complex transcriptional network that results in the establishment and
maintenance of the muscle phenotype. To begin to determine how the
expression of MRF4 is regulated by other muscle-specific
transcription factors, we have isolated a region of the MRF4 gene that confers muscle-specific expression and have analyzed
this promoter region for cis-acting elements involved in trans-activation by the myogenic bHLH and MEF2 transcription
factors. Here, we show that in 10T1/2 fibroblasts the MRF4 promoter is trans-activated by myogenin, MyoD, myf5, and
by the MEF2 factors, but that MRF4 does not activate expression of its
own promoter. Myogenin activated the MRF4 promoter directly by
an E box-dependent mechanism, while MEF2 factors activated the promoter
through an indirect pathway. The E box-dependent regulation of the MRF4 promoter is in contrast to the regulation of the myogenin and MyoD promoters and may represent a
mechanism for the differential expression of these factors during
myogenesis.
Volume 270,
Number 7,
Issue of February 17, 1995 pp. 2889-2892
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
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