Relationship between nucleosome positioning and DNA methylation

By Ramakrishna K. Chodavarapu, Suhua Feng, Yana V. Bernatavichute, Pao-Yang Chen, Hume Stroud, Yanchun Yu, Jonathan Hetzel, F. Kuo, Jin Kim, Shawn Cokus and 9 more. Nature, 2010

742 citations recorded by the source corpus.

Nucleosomes compact and regulate access to DNA in the nucleus, and are composed of approximately 147 bases of DNA wrapped around a histone octamer. Here we report a genome-wide nucleosome positioning analysis of Arabidopsis thaliana using massively parallel sequencing of mononucleosomes. By combining this data with profiles of DNA methylation at single base resolution, we identified 10-base periodicities in the DNA methylation status of nucleosome-bound DNA and found that nucleosomal DNA was more highly methylated than flanking DNA. These results indicate that nucleosome positioning influences DNA methylation patterning throughout the genome and that DNA methyltransferases preferentially target nucleosome-bound DNA. We also observed similar trends in human nucleosomal DNA, indicating that the relationships between nucleosomes and DNA methyltransferases are conserved. Finally, as has been observed in animals, nucleosomes were highly enriched on exons, and preferentially positioned at intron–exon and exon–intron boundaries. RNA polymerase II (Pol II) was also enriched on exons relative to introns, consistent with the hypothesis that nucleosome positioning regulates Pol II processivity. DNA methylation is also enriched on exons, consistent with the targeting of DNA methylation to nucleosomes, and suggesting a role for DNA methylation in exon definition.

Subfields: Molecular Biology, Plant Science

View Paper: https://www.semanticscholar.org/paper/b35569b14e96322914f49a34cf6e483011a36e8c

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

In Plant Science

Citations in the corpus

High-resolution genome-wide DNA methylation maps of mouse primary female dermal fibroblasts and keratinocytes (2014, positive): “Periodicity of correlation for the methylation of neighboring CG dinucleotides was also observed previously in the Arabidopsis and honey bee genomes [4,21,32].”
Widespread dynamic DNA methylation in response to biotic stress (2012, background): “At the molecular level, DNA methylation is coupled to nucleosome positioning (1), specific histone modifications (2), and transcriptional activity (3, 4).”
Epigenetics in alternative pre-mRNA splicing (2011, positive): “…are positioned nonrandomly along genes and are particularly enriched at intron-exon junctions, thus marking exons (Andersson et al., 2009; Chodavarapu et al., 2010; Dhami et al., 2010; Kolasinska-Zwierz et al., 2009; Nahkuri et al., 2009; Ponts et al., 2008; Schwartz et al., 2009; Spies…”
DNA methylation: superior or subordinate in the epigenetic hierarchy? (2011, background): “Genomewide nucleosome positioning analysis in Arabidopsis thaliana and human cells also showed that DNA methylation is enriched in nucleosome-bound DNA rather than linker DNA, indicating that nucleosome-bound DNA is a preferred substrate for DNA methylation.(83) Nucleosome positioning displays a seq”
Integrative epigenomic mapping defines four main chromatin states in Arabidopsis (2011, background): “Collectively, the 12 chromatin marks cover almost all of the regions that are detectably associated with histone H3, which amount to B90% of the total genome sequence (data not shown; Chodavarapu et al, 2010).”
Cell-free DNA comprises an in vivo nucleosome footprint that informs its tissues-of-origin (2016, neutral): “Nucleosomes are known to be well-positioned in relation to landmarks of gene regulation, e.g. transcriptional start sites (Pedersen et al., 2014) and exon-intron boundaries (Andersson et al., 2009; Chodavarapu et al., 2010).”