Abstract
A strong correlation between nucleosome positioning and DNA methylation patterns has been reported in literature. However, the mechanistic model accounting for the correlation remains elusive. In this study, we evaluated the effects of specific DNA methylation patterns on modulating nucleosome conformation and stability using FRET and SAXS. CpG dinucleotide repeats at 10 bp intervals were found to play different roles in nucleosome stability dependent on their methylation states and their relative nucleosomal locations. An additional (CpG)5 stretch located in the nucleosomal central dyad does not alter the nucleosome conformation, but significant conformational differences were observed between the unmethylated and methylated nucleosomes. These findings suggest that the correlation between nucleosome positioning and DNA methylation patterns can arise from the variations in nucleosome stability dependent on their sequence and epigenetic content. This knowledge will help to reveal the detailed role of DNA methylation in regulating chromatin packaging and gene transcription.
Highlights
A strong correlation between nucleosome positioning and DNA methylation patterns has been reported in literature
Unmethylated CpG dinucleotides predominantly exist in the minor grooves of the nucleosomal DNA facing away from the histone octamer, while methylated CpG dinucleotides dominate in the minor grooves of the nucleosomal DNA facing towards the histone octamer[7,8]
We introduced three specific CpG patterns in this study, namely 1) (CpG)[5] located in the Central Dyad; 2) 5 3 CpG dinucleotides at 10 bp intervals located in the Major Grooves; and 3) 5 3 CpG dinucleotides at 10 bp intervals located in the Minor Grooves
Summary
A strong correlation between nucleosome positioning and DNA methylation patterns has been reported in literature. An additional (CpG)[5] stretch located in the nucleosomal central dyad does not alter the nucleosome conformation, but significant conformational differences were observed between the unmethylated and methylated nucleosomes These findings suggest that the correlation between nucleosome positioning and DNA methylation patterns can arise from the variations in nucleosome stability dependent on their sequence and epigenetic content. Several studies have found that elder people have higher methylation levels in comparison to young adults, and males have higher global DNA methylation levels compared to females[4] It is well-established that CpG methylation located in the promoter region plays a vital role in gene regulation. DNA bases located in this region are more susceptible to nuclease digestion and exhibit a less distorted conformation as compared with other nucleosomal DNA regions[17,18]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
