Formation and properties of hairpin and tetraplex structures of guanine-rich regulatory sequences of muscle-specific genes.
Clustered guanine residues in DNA readily generate hairpin or a variety of tetrahelical structures. The myogenic determination protein MyoD was reported to bind to a tetrahelical structure of guanine-rich enhancer sequence of muscle creatine kinase (MCK) more tightly than to its target E-box motif [K. Walsh and A. Gualberto (1992) J. Biol. Chem., 267, 13714-13718], suggesting that tetraplex structures of regulatory sequences of muscle-specific genes could contribute to transcriptional regulation. In the current study we show that promoter or enhancer sequences of various muscle-specific genes display a disproportionately high incidence of guanine clusters. The sequences derived from the guanine-rich promoter or enhancer regions of three muscle-specific genes, human sarcomeric mitochondrial creatine kinase (sMtCK), mouse MCK and alpha7 integrin formed diverse secondary structures. The sMtCK sequence folded into a hairpin structure; the alpha7 integrin oligonucleotide generated a unimolecular tetraplex; and sequences from all three genes associated to generate bimolecular tetraplexes. Furthermore, two neighboring non-contiguous guanine-rich tracts in the alpha7 integrin promoter region also paired to form a tetraplex structure. We also show that homodimeric MyoD bound bimolecular tetraplex structures of muscle-specific regulatory sequences more efficiently than its target E-box motif. These results are consistent with a role of tetrahelical structures of DNA in the regulation of muscle-specific gene expression.
Yafe
Anat
A
Department of Biochemistry, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology PO Box 9649 Bat Galim, Haifa 31096, Israel.
Etzioni
Shulamit
S
Weisman-Shomer
Pnina
P
Fry
Michael
M
D015703:Antigens, CD / Q000235:genetics; D001483:Base Sequence; D003402:Creatine Kinase / Q000235:genetics; D052283:Creatine Kinase, MM Form; D052281:Creatine Kinase, Mitochondrial Form; D004247:DNA / Q000737:chemistry*; D024721:E-Box Elements; D004742:Enhancer Elements, Genetic; D054856:G-Quadruplexes; D006147:Guanine / Q000032:analysis*; D039001:Integrin alpha Chains / Q000235:genetics; D007527:Isoenzymes / Q000235:genetics; D008969:Molecular Sequence Data; D009132:Muscles / Q000378:metabolism*; D017570:MyoD Protein / Q000378:metabolism; D009690:Nucleic Acid Conformation; D011166:Porphyrins / Q000737:chemistry; D011401:Promoter Regions, Genetic; D013696:Temperature
D015703:Antigens, CD; D039001:Integrin alpha Chains; D007527:Isoenzymes; D017570:MyoD Protein; D011166:Porphyrins; C085725:integrin alpha7; D006147:Guanine; D004247:DNA; D003402:Creatine Kinase; D052283:Creatine Kinase, MM Form; D052281:Creatine Kinase, Mitochondrial Form