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Identification of a G-quadruplex forming sequence in the promoter of UCP1

Journal article
Authors Y. B. Zhao
Jay Uhler
Published in Acta Biochimica Et Biophysica Sinica
Volume 50
Issue 7
Pages 718-722
ISSN 1672-9145
Publication year 2018
Published at Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Pages 718-722
Language en
Links dx.doi.org/10.1093/abbs/gmy059
Keywords G-quadruplex, UCP1, TMPyP4, promoter, brown adipose-tissue, c-myc, dna, thermogenesis, transcription, therapeutics, adipocytes, metabolism, telomere, disease, Biochemistry & Molecular Biology, Biophysics, ates of america, v107, p16072
Subject categories Medical cell biology

Abstract

G-quadruplexes are higher-order nucleic acid structures formed in G-rich sequences in DNA or RNA. G-quadruplexes are distributed in many locations in the human genome, including promoter regions, and are viewed as promising therapeutic targets. Uncoupling protein-1 (UCP1) is a mitochondrial thermogenic gene critical for energy expenditure in the form of heat in the brown adipose tissue. UCP1 is only expressed during brown fat cell differentiation and is a candidate target for treating obesity. However, the regulation of UCP1 expression is not clear. We reported here that a G-quadruplex forming sequence exists in the promoter of UCP1. The 5,10,15,20-tetra(Nmethyl- 4-pyridyl) porphyrin (TMPyP4) enhanced cellular expression of UCP1 and destabilized the G-quadruplex formed by the sequence from the promoter of UCP1. Mutations in the G-quadruplex regulated the cellular activity of UCP1 promoter as evidenced by a UCP1-promoter luciferase assay. These results suggest that G-quadruplex structure is a potential target to regulate the expression of UCP1.

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