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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

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.

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Official URL: http://dx.doi.org/10.1021/acs.jmedchem.6b00453

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
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
Depositing User: Id for Latest eprints
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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