Systematic Motif Analysis of
G-quadruplex Regulatory Regions in Breast Cancer

Abstract

G-quadruplex (G4) complex is a secondary DNA structure formed in sequences that are rich in guanine and are expressed in various regions of eukaryotic sequence. Using G4-ChIP-seq data from more than 20 patient-derived tumor xenograft (PDTX) models from a literature, the sequence with the most commonly occurring G-rich regions/motifs were selected. Three patients out of the 20+ patients were randomly selected and screened for G4 motif from the ChIP-seq data. Our project aims to identify the sequence characteristics and regulatory elements of G4 DNA motifs in breast cancer-associated genes. We hypothesize that G4-forming sequences may influence the behavior of regulatory components nearby onco-related genes, such as c-MYC gene.

Introduction

G4 structures are non-canonical DNA secondary structures formed by guanine-rich sequences that could be folded into a stable four-stranded configuration as shown in Figure 1 [1] . These structures have been recognized as important regulatory elements in the human genome for cell proliferation and cancer progression [2]. G4 complexes are also found in the form of RNA in the case of patients with Amyotrophic Lateral Sclerosis (ALS) also known as Lou Gehrig's disease [3]. These complexes may trap nearby endogenous regulatory proteins in neuronal cells and inhibit their function leading to progression of the disease [4].

Figure 1. A) Schematic of an intra-molecular G4 DNA structure consisting of three G-quartets. B) The typical G4 DNA motif sequence has four G-tracts of three guanines separated by loop regions. The figure was cited from [1].

These seemingly random aggregation of these complexes may play important regulatory roles in the human genome to either help repress and/or enhance the expression of certain genes [5, 6]. As mentioned previously, literature has indicated the involvement of G4 quadruplex in various cancers [7]. The genomic context of these regulatory elements remains elusive and requires further investigation.