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Relationship between nucleosome positioning and DNA methylation

Abstract

Nucleosomes compact and regulate access to DNA in the nucleus, and are composed of approximately 147 bases of DNA wrapped around a histone octamer1,2. 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.

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Figure 1: Characterization of A. thaliana nucleosome data.
Figure 2: DNA methylation profiles of nucleosome-bound DNA in Arabidopsis.
Figure 3: DNA methylation profiles of nucleosome-bound DNA in humans.
Figure 4: Nucleosome and Pol II levels in exons.

Accession codes

Primary accessions

Gene Expression Omnibus

Data deposits

All sequencing files have been deposited in GEO under accession code GSE21673.

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Acknowledgements

We thank members of our laboratories for input and guidance, and the Department of Energy, Institute for Genomics and Proteomics for support. R.K.C. is supported by NIH training grant GM07104. S.F. is a Howard Hughes Medical Institute Fellow of the Life Sciences Research Foundation. P.-Y.C. is funded by Eli & Edythe Broad Center of Regenerative Medicine & Stem Cell Research at UCLA. M.B. was supported by an Alexander-von-Humboldt Fellowship and U.K. by a Heisenberg Fellowship. X.Z. was supported by a Faculty Research Grant (JR-040) from the University of Georgia. Research was supported by an Innovation Award from the Eli & Edythe Broad Center of Regenerative Medicine & Stem Cell Research at UCLA, NIH grants GM60398 and GM42143, and NSF Plant Genome Research Program #0701745. S.E.J. is an Investigator of the Howard Hughes Medical Institute.

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Contributions

S.E.J. and M.P. designed the research. S.F., Y.V.B., H.S., Y.Y., J.A.H., M.B., P.H., A.T.C., U.K., S.S.M. and X.Z. performed experiments. R.K.C., P.-Y.C, F.K., J.K., S.J.C and D.C. analysed data. R.K.C., S. F., S.E.J. and M.P. wrote the paper.

Corresponding authors

Correspondence to Steven E. Jacobsen or Matteo Pellegrini.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains Supplementary Methods and Supplementary Figures 1-24 with legends. (PDF 1091 kb)

Supplementary Table 1

The table shows the number of unique hits per million, for Arabidopsis genes greater than 1000 bases long, in wild type shoots. (XLS 2298 kb)

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Chodavarapu, R., Feng, S., Bernatavichute, Y. et al. Relationship between nucleosome positioning and DNA methylation. Nature 466, 388–392 (2010). https://doi.org/10.1038/nature09147

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