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

转移抑制因子 NM23-H2 与 c-MYC 启动子核酸酶高敏元件内的 G-四链体 DNA 相互作用诱导 c-MYC 表达

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作者:Ram Krishna Thakur, Praveen Kumar, Kangkan Halder, Anjali Verma, Anirban Kar, Jean-Luc Parent, Richa Basundra, Akinchan Kumar, Shantanu Chowdhury

Abstract

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.

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