RT Journal
A1 Lay, Fides D.
A1 Triche, Timothy J.
A1 Tsai, Yvonne C.
A1 Su, Sheng-Fang
A1 Martin, Sue Ellen
A1 Daneshmand, Siamak
A1 Skinner, Eila C.
A1 Liang, Gangning
A1 Chihara, Yoshitomo
A1 Jones, Peter A.
T1 Reprogramming of the human intestinal epigenome by surgical tissue transposition
JF Genome Research 
JO Genome Research 
YR 2014 
FD April 01 
VO 24 
IS 4 
SP 545 
OP 553 
DO 10.1101/gr.166439.113 
UL http://genome.cshlp.org/content/24/4/545.abstract 
AB Extracellular cues play critical roles in the establishment of the epigenome during development and may also contribute to epigenetic perturbations found in disease states. The direct role of the local tissue environment on the post-development human epigenome, however, remains unclear due to limitations in studies of human subjects. Here, we use an isogenic human ileal neobladder surgical model and compare global DNA methylation levels of intestinal epithelial cells pre- and post-neobladder construction using the Infinium HumanMethylation450 BeadChip. Our study is the first to quantify the effect of environmental cues on the human epigenome and show that the local tissue environment directly modulates DNA methylation patterns in normal differentiated cells in vivo. In the neobladder, the intestinal epithelial cells lose their tissue-specific epigenetic landscape in a time-dependent manner following the tissue’s exposure to a bladder environment. We find that de novo methylation of many intestine-specific enhancers occurs at the rate of 0.41% per month (P < 0.01, Pearson = 0.71), while demethylation of primarily non-intestine-specific transcribed regions occurs at the rate of −0.37% per month (P < 0.01, Pearson = −0.57). The dynamic resetting of the DNA methylome in the neobladder not only implicates local environmental cues in the shaping and maintenance of the epigenome but also illustrates an unexpected cross-talk between the epigenome and the cellular environment.