A Mechanosensor Mechanism Controls the G-Quadruplex/i-Motif Molecular Switch in the MYC Promoter NHE III1
| Autor: | Laurence H. Hurley, Caleb Sutherland, Hanbin Mao, Yunxi Cui |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Molecular switch Oncogene General Chemistry 010402 general chemistry medicine.disease_cause G-quadruplex Mutually exclusive events 01 natural sciences Biochemistry Molecular biology Transcription Activation Catalysis 0104 chemical sciences Cell biology 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology Colloid and Surface Chemistry chemistry medicine Carcinogenesis Cytosine DNA |
| Zdroj: | Journal of the American Chemical Society. 138:14138-14151 |
| ISSN: | 1520-5126 0002-7863 |
| Popis: | MYC is overexpressed in many different cancer types and is an intensively studied oncogene because of its contributions to tumorigenesis. The regulation of MYC is complex, and the NHE III1 and FUSE elements rely upon noncanonical DNA structures and transcriptionally induced negative superhelicity. In the NHE III1 only the G-quadruplex has been extensively studied, whereas the role of the i-motif, formed on the opposite C-rich strand, is much less understood. We demonstrate here that the i-motif is formed within the 4CT element and is recognized by hnRNP K, which leads to a low level of transcription activation. For maximal hnRNP K transcription activation, two additional cytosine runs, located seven bases downstream of the i-motif-forming region, are also required. To access these additional runs of cytosine, increased negative superhelicity is necessary, which leads to a thermodynamically stable complex between hnRNP K and the unfolded i-motif. We also demonstrate mutual exclusivity between the MYC G-qua... |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|