Nucleic Acids Research Advance Access published online on May 29, 2008
Nucleic Acids Research, doi:10.1093/nar/gkn340
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Molecular Biology |
Differential binding of quadruplex structures of muscle-specific genes regulatory sequences by MyoD, MRF4 and myogenin
Department of Biochemistry, Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, POB 9649 Bat Galim, Haifa 31096, Israel
*To whom correspondence should be addressed. Tel: +972 4 829 5328; Fax: +972 4 851 0735; Email: mickey{at}tx.technion.ac.il
Received April 3, 2008. Revised April 27, 2008. Accepted May 11, 2008.
Four myogenic regulatory factors (MRFs); MyoD, Myf-5, MRF4 and Myogenin direct muscle tissue differentiation. Heterodimers of MRFs with E-proteins activate muscle-specific gene expression by binding to E-box motifs d(CANNTG) in their promoters or enhancers. We showed previously that in contrast to the favored binding of E-box by MyoD-E47 heterodimers, homodimeric MyoD associated preferentially with quadruplex structures of regulatory sequences of muscle-specific genes. To inquire whether other MRFs shared the DNA binding preferences of MyoD, the DNA affinities of hetero- and homo-dimeric MyoD, MRF4 and Myogenin were compared. Similarly to MyoD, heterodimers with E47 of MRF4 or Myogenin bound E-box more tightly than quadruplex DNA. However, unlike homodimeric MyoD or MRF4, Myogenin homodimers associated weakly and nonpreferentially with quadruplex DNA. By reciprocally switching basic regions between MyoD and Myogenin we demonstrated dominance of MyoD in determining the quadruplex DNA-binding affinity. Thus, Myogenin with an implanted MyoD basic region bound quadruplex DNA nearly as tightly as MyoD. However, a grafted Myogenin basic region did not diminish the high affinity of homodimeric MyoD for quadruplex DNA. We speculate that the dissimilar interaction of MyoD and Myogenin with tetrahelical domains in muscle gene promoters may differently regulate their myogenic activities.
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors
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