Kaulage, Mangesh and Maji, Basudeb and Bhat, Jyotsna and Iwasaki, Yasumasa and Chatterjee, Subhrangsu and Bhattacharya, Santanu and Muniyappa, K (2016) Discovery and Structural Characterization of G-quadruplex DNA in Human Acetyl-CoA Carboxylase Gene Promoters: Its Role in Transcriptional Regulation and as a Therapeutic Target for Human Disease. In: JOURNAL OF MEDICINAL CHEMISTRY, 59 (10). pp. 5035-5050.
Full text not available from this repository. (Request a copy)Abstract
Accumulating evidence suggests that G-quadruplexes play vital roles in gene expression, DNA replication, and recombination. Three distinct promoters (PI, PII, and PIII) regulate human acetyl-CoA carboxylase 1 (ACC1) gene expression. In this study, we asked whether the G-rich sequences within the human ACC1 (PI and PII) promoters can form G-quadruplex structures and regulate normal DNA transactions. Using multiple complementary methods, we show that G-rich sequences of PI and PII promoters form intramolecular G-quadruplex structures and then establish unambiguously the topologies of these structures. Importantly, G-quadruplex formation in ACC1 gene promoter region blocks DNA replication and suppresses transcription, and this effect was further augmented by G-quadruplex stabilizing ligands. Altogether, these results are consistent with the notion that G-quadruplex structures exist within the human ACC1 gene promoter region, whose activity can be suppressed by G-quadruplex stabilizing ligands, thereby revealing a novel regulatory mechanism of ACC1 gene expression and as a possible therapeutic target.
| Item Type: | Journal Article |
|---|---|
| Publication: | JOURNAL OF MEDICINAL CHEMISTRY |
| Publisher: | AMER CHEMICAL SOC |
| Additional Information: | Copy right for this article belongs to the AMER CHEMICAL SOC, 1155 16TH ST, NW, WASHINGTON, DC 20036 USA |
| Department/Centre: | Division of Biological Sciences > Biochemistry Division of Chemical Sciences > Organic Chemistry |
| Date Deposited: | 30 Jun 2016 05:07 |
| Last Modified: | 30 Jun 2016 05:07 |
| URI: | http://eprints.iisc.ac.in/id/eprint/54091 |
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