Transcriptional Regulation of the Xenopus MyoD Gene

MyoD is one of the MRFs (Muscle Regulatory Factors) and it
functions to determine the muscle cell fate. The mechanism by which
MyoD regulates the muscle development program is very well
understood. However, the transcriptional regulation of the MyoD
gene itself has not studied in Xenopus. In this thesis, I have
analyzed the transcriptional regulatory mechanism of the MyoD gene
in Xenopus by different approaches, which include transgenic
reporter analysis of its cis-regulatory elements of MyoD
transcription and gain-of-function and loss-of-function tests of
several potential regulaters. Here I showed that the expression of
the XmyoD gene is controlled by a combination of induction,
repression and maintenance. One activating motif, one repressing
motif and one maintenance motif were found by transgenic reporter
analysis. XSRF (Xenopus serum response factor) binds with the
maintenance enhancer to maintain the expression of XmyoD gene. A
repetitive DNA sequence was discovered in the -2.8/-2.0kb region in
the XmyoD genomic sequence. The repetitive DNA sequence in the
XmyoD gene locus may produce sense and anti-sense transcripts. In
addition, several potential regulators have been analyzed. It has
been shown that XSEB-4, a direct target of XmyoD protein, is able
to induce the expression of XmyoD gene. Xenopus Ying Yang 1 (XYY1)
can repress the expression of the XmyoD gene. Lef-1 is necessary
and sufficient for the expression of XmyoD gene. This provides
strong evidence that Lef-1 is the transcription factor of the
zygotic Wnt signaling pathway that activates the expression of the
XmyoD gene.