Analysis Of Relationships Between Nucleosome Postioning And G-quadruplex

Nucleosomes is the basic unit of chromatins in eukaryotes,nucleosome postioning and histone modification cooperate to regulate the gene transcription.In recent years,many reaserch reveals that the nucleosome occupancy and histone modifications have certain distribution patterns around the transcription start site.G-quadruplexes are nucleic acid secondary structure form by hydrogen bonding arise in guanine-rich DNA or RNA sequences.The G-quadruplexes are enriched in genomic regions such as telomeres,promoters and 5' untranglated regions(5'UTR),which suggest that they are involved in a broad range of biological processes as gene replication and recombination,telomeres extends and transcriptional regulation,etc.The analysis performed by sequence motif is not accurate because of the dynamic positioning of nucleosomes and G-quadruplexes in vivo.With the rapid development of high throughput sequencing technology,we are able to access the whole genome G-quadruplex sequencing data.We analyzed their role in gene expression and genetic/epigenetic instability with nucleosome positioning,histone modifications and chromatin three-dimensional conformation.We analyzed the relationships of G-quadruplexes,nucleosome postioning and epigenetic modifications around whole genome.Firstly,we explored the distribution of G-quadruplexes,found that G-quadruplexes tend to form in the open chromatin,also significantly enriched in some cis-regulatory elements such as promoter,5'UTR and splice site.Then we discovered diverse pattems of nucleosome occupancy around G-quadruplexes shows nucleosome deplete around stable G-quadruplex sites but nucleosome occupancy are more pervasive around unstable G-quadruplex sites.When observing different histone modifications around G-quadruplexes,found that G-quadruplex recruit H3K4me3 and H3K27ac marks(associate with Active promoters and enhancers)but lack of H3K27me3 mark(associate with sliencer).The formation areas of G-quadruplexes often enriched CpG islands,whereas the proportion of methylation is reduced,which demonstrating that G-quadruplexes is inhibition of DNA methylation.According to specific patterns of G-quadruplexes occupancy around TSS and associated with expression level of target genes.We found that the formation of G-quadruplex lead to nucleosome depleted at regions upstream of the TSS,and making the regions accessible for the transcription factory especially for G-quadruplexes on template strand.Furthermore,consider to the regions of TSS downstream,the G-quadruplexes formed on coding strand helps DNA maintain unwinding condition,on the contrary the presence of G-quadrupjexes on template strand induce polymerase stalling resulting in inhibit transcription.In addition,we systematically investigated the relationship between G-quadruplex and chromatin conformation,and found the G-quadruplexes are significantly enriched around chromatin conformation domain boundaries.The chromatin condensation inside the highly intraconnected topologically associated domains(TAD)inaccessible for G-quadruplex formation.The TAD boundary areas usually concentrate gene regulatory elements such as enhancers,silencers and promoters.In conclusion,G-quadruplex structure could influence the nucleosome positioning,histone modifications,and distal regulatory elements.We integrated varies of sequencing data to construct the model of G-quadruplex participate in transcription regulating,and may shed light on later study.