Metastases suppressor NM23-H2 interaction with G-quadruplex DNA within c-MYC promoter nuclease hypersensitive element induces c-MYC expression

Regulatory influence of the G-quadruplex or G4 motif present within the nuclease hypersensitive element (NHE) in the promoter of c-MYC has been noted. On the other hand, association of NM23-H2 to the NHE leads to c-MYC activation. Therefore, NM23-H2 interaction with the G4 motif within the c-MYC NHE...

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Bibliographic Details
Published in:Nucleic acids research 2009-01, Vol.37 (1), p.172-183
Main Authors: Thakur, Ram Krishna, Kumar, Praveen, Halder, Kangkan, Verma, Anjali, Kar, Anirban, Parent, Jean-Luc, Basundra, Richa, Kumar, Akinchan, Chowdhury, Shantanu
Format: Article
Language:English
Subjects:
Binding Sites
Cell Line
Deoxyribonucleases - metabolism
DNA - chemistry
G-Quadruplexes
Genes, myc
Humans
Molecular Biology
Mutation
NM23 Nucleoside Diphosphate Kinases - genetics
NM23 Nucleoside Diphosphate Kinases - metabolism
Promoter Regions, Genetic
Proto-Oncogene Proteins c-myc - biosynthesis
Transcriptional Activation
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Summary:Regulatory influence of the G-quadruplex or G4 motif present within the nuclease hypersensitive element (NHE) in the promoter of c-MYC has been noted. On the other hand, association of NM23-H2 to the NHE leads to c-MYC activation. Therefore, NM23-H2 interaction with the G4 motif within the c-MYC NHE presents an interesting mechanistic possibility. Herein, using luciferase reporter assay and chromatin immunoprecipitation we show NM23-H2 mediated c-MYC activation involves NM23-H2-G4 motif binding within the c-MYC NHE. G4 motif complex formation with recombinant NM23-H2 was independently confirmed using fluorescence energy transfer, which also indicated that the G4 motif was resolved to an unfolded state within the protein-bound complex. Taken together, this supports transcriptional role of NM23-H2 via a G4 motif.
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/gkn919