RT Journal
A1 Lay, Fides D.
A1 Liu, Yaping
A1 Kelly, Theresa K.
A1 Witt, Heather
A1 Farnham, Peggy J.
A1 Jones, Peter A.
A1 Berman, Benjamin P.
T1 The role of DNA methylation in directing the functional organization of the cancer epigenome
JF Genome Research 
JO Genome Research 
YR 2015 
FD April 01 
VO 25 
IS 4 
SP 467 
OP 477 
DO 10.1101/gr.183368.114 
UL http://genome.cshlp.org/content/25/4/467.abstract 
AB The holistic role of DNA methylation in the organization of the cancer epigenome is not well understood. Here we perform a comprehensive, high-resolution analysis of chromatin structure to compare the landscapes of HCT116 colon cancer cells and a DNA methylation-deficient derivative. The NOMe-seq accessibility assay unexpectedly revealed symmetrical and transcription-independent nucleosomal phasing across active, poised, and inactive genomic elements. DNA methylation abolished this phasing primarily at enhancers and CpG island (CGI) promoters, with little effect on insulators and non-CGI promoters. Abolishment of DNA methylation led to the context-specific reestablishment of the poised and active states of normal colon cells, which were marked in methylation-deficient cells by distinct H3K27 modifications and the presence of either well-phased nucleosomes or nucleosome-depleted regions, respectively. At higher-order genomic scales, we found that long, H3K9me3-marked domains had lower accessibility, consistent with a more compact chromatin structure. Taken together, our results demonstrate the nuanced and context-dependent role of DNA methylation in the functional, multiscale organization of cancer epigenomes.