Epigenomic features of DNA G-quadruplexes and their roles in regulating rice gene transcription

Abstract

A DNA G-quadruplex (G4) is a non-canonical four-stranded nucleic acid structure involved in many biological processes in mammals. The current knowledge on plant DNA G4s, however, is limited; whether and how DNA G4s impact gene expression in plants is still largely unknown. Here, we applied a protocol referred to as BG4-DNA-IP-seq followed by a comprehensive characterization of DNA G4s in rice (Oryza sativa L.); we next integrated dG4s (experimentally detectable G4s) with existing omics data and found that dG4s exhibited differential DNA methylation between TE (transposable element) and non-TE (non-transposable element) genes. dG4 regions displayed genic-dependent enrichment of epigenomic signatures; finally, we showed that these sites displayed a positive association with expression of DNA G4-containing genes when located at promoters, and a negative association when located in the gene body, suggesting localization-dependent promotional/repressive roles of DNA G4s in regulating gene transcription. This study reveals interrelations between DNA G4s and epigenomic signatures, as well as implicates DNA G4s in modulating gene transcription in rice. Our study provides valuable resources for the functional characterization or bioengineering of some of key DNA G4s in rice.

Epigenomic Features and Potential Functions of K+ and Na+ Favorable DNA G-Quadruplexes in Rice

“…It is one of the most studied non-B DNA structures in eukaryotic genomes, especially in humans. G4s have been found to preferentially form in various functional genomic regions [ 5 , 6 ], including telomeres [ 3 , 7 , 8 , 9 , 10 , 11 ], rDNA loci [ 12 , 13 ], promoters [ 6 , 14 , 15 ], and the first introns of human genes [ 16 ].…”

“…It has been reported that DNA G4s play regulatory roles in modulating the expression of certain genes, thereby being involved in various biological processes [ 15 , 17 , 18 , 19 , 20 , 21 , 22 ]. They include, but are not limited to, DNA replication [ 10 , 23 ], immunoglobulin switch recombination [ 24 ], telomere maintenance [ 10 , 11 ], genome instability [ 10 , 25 ], gene transcription [ 6 , 15 , 26 , 27 , 28 ], reprogramming of DNA or chromatin modifications [ 29 , 30 ], human stem cell differentiation [ 31 ], and human diseases [ 32 , 33 ]. In particular, they can be considered as potential drug targets for human disease treatment [ 11 , 25 , 34 , 35 ], which attracts more attention and boosts G4 studies in pharmacogenomics.…”

“…The presence of putative G-quadruplex sequences (PQSs) in DNAs or RNAs mainly relies on computational screening in most plant species [ 20 , 41 , 42 , 43 ], including Arabidopsis [ 44 ], and grass species, such as maize [ 45 ], rice [ 46 ], wheat [ 47 ], and barley [ 48 ]. In addition, very limited studies of plant G4s showed that G4s may play potential roles in regulating various physiological processes in plants, such as gene expression and translation, and in response to various stresses [ 15 , 20 , 28 , 47 , 49 , 50 , 51 ]. However, the global identification of G4s in vitro has only been conducted using G4-seq in Arabidopsis [ 40 , 52 ], and BG4-DNA-IP-seq (DNA immunoprecipitation with anti-BG4 antibody coupled with sequencing) in rice [ 15 ].…”

The Newly Sequenced Genome of Pisum sativum Is Replete with Potential G-Quadruplex-Forming Sequences—Implications for Evolution and Biological Regulation

“…A recent study showed the distinct roles of G4 in the transcription regulation of the rice genome based on its genomic localization. G4 found in promoters had a potentized effect, whereas gene location caused repression of gene transcription [ 11 ].…”

“…The presence of G4s has been demonstrated in viral [ 12 , 13 ], bacterial [ 14 ], archaeal [ 15 ], fungal [ 16 , 17 ], and other eukaryotic genomes, including that of humans [ 18 ]. However, only a few genome-wide analyses of G4s in plants have been reported [ 11 , 19 , 20 , 21 , 22 ]. Genome-wide analyses of G4s have not been reported for P. sativum, the genome of which was sequenced and assembled 3 years ago [ 23 ].…”