G-quadruplexes are four-stranded helical nucleic acid structures formed by 
guanine-rich sequences. A considerable number of studies have revealed that 
these noncanonical structural motifs are widespread throughout the genome and 
transcriptome of numerous organisms, including humans. In particular, 
G-quadruplexes occupy strategic locations in genomic DNA and both coding and 
noncoding RNA molecules, being involved in many essential cellular and 
organismal functions. In this review, we first outline the fundamental 
structural features of G-quadruplexes and then focus on the concept that these 
DNA and RNA structures convey a distinctive layer of epigenetic information that 
is critical for the complex regulation, either positive or negative, of 
biological activities in different contexts. In this framework, we summarize and 
discuss the proposed mechanisms underlying the functions of G-quadruplexes and 
their interacting factors. Furthermore, we give special emphasis to the 
interplay between G-quadruplex formation/disruption and other epigenetic marks, 
including biochemical modifications of DNA bases and histones, nucleosome 
positioning, and three-dimensional organization of chromatin. Finally, 
epigenetic roles of RNA G-quadruplexes in post-transcriptional regulation of 
gene expression are also discussed. Undoubtedly, the issues addressed in this 
review take on particular importance in the field of comparative epigenetics, as 
well as in translational research.