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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Human-specific features of the G-quadruplex in the androgen receptor gene promoter: A comparative structural and dynamics study

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Author(s):
Solis-Calero, Christian [1] ; Augusto, Taize M. [1] ; Carvalho, Hernandes F. [1]
Total Authors: 3
Affiliation:
[1] Univ Estadual Campinas, Dept Struct & Funct Biol, Campinas, SP - Brazil
Total Affiliations: 1
Document type: Journal article
Source: JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY; v. 182, p. 95-105, SEP 2018.
Web of Science Citations: 1
Abstract

The androgen receptor (AR) promoter contains guanine-rich regions that are able to fold into polymorphic G-quadruplex (GQ) structures, and whose deletion decreases AR gene transcription. Our attention was focused on this region because of the frequent termination of sequencing reactions during promoter methylation studies. UV and circular dichroism (CD) spectroscopy of synthetic oligonucleotides encompassing these guanine-rich regions suggested a parallel quadruplex topology with three guanine quartets and three side loops in the three cases. Melting curves revealed a lower thermostability of the human GQ compared to the rat/mouse QG structures, which is attributed to the presence of a longer central loop in the former. One molecular model is proposed for the highly similar sequences in the rat/mouse. Due to the polymorphism resulting from possible arrangements of the guanine tracts, two models were derived for the human GQ. Molecular dynamics (MD) simulations determined that both models for the human GQ had higher flexibility and lower stability than the rodent GQ models. These properties result from the presence of a longer central loop in the human GQ models, which contains 11 and 13 nucleotides, in comparison to the 2-nucleotide long loop in the rat/mouse GQ. Overall, the unveiled structural and dynamics features provide sufficient detail for the intelligent design of drugs targeting the human AR promoter. (AU)

FAPESP's process: 09/16150-6 - Androgen regulation, sinalization and cellular interactions in prostate development, physiology and regression
Grantee:Hernandes Faustino de Carvalho
Support Opportunities: Research Projects - Thematic Grants