@article{Lay01042015,
author = {Lay, Fides D. and Liu, Yaping and Kelly, Theresa K. and Witt, Heather and Farnham, Peggy J. and Jones, Peter A. and Berman, Benjamin P.}, 
title = {The role of DNA methylation in directing the functional organization of the cancer epigenome},
volume = {25}, 
number = {4}, 
pages = {467-477}, 
year = {2015}, 
doi = {10.1101/gr.183368.114}, 
abstract ={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.}, 
URL = {http://genome.cshlp.org/content/25/4/467.abstract}, 
eprint = {http://genome.cshlp.org/content/25/4/467.full.pdf+html}, 
journal = {Genome Research} 
}