Whole genome bisulfite sequencing enabled quantitative single
base-resolution DNA methylation profiling of the extraembryonic compartment. The
data were compared to equivalent analyses of embryonic, fetal, and adult (normal
and cancer) samples. (A) Principal component analysis segregated the
extraembryonic samples from all others primarily along PC1. Within the
extraembryonic group, the samples separated according to type and gestational
age. The exception was the smooth chorion, which contains a cytotrophoblast
progenitor population pregnancy. (B) Chromosome-level (Chr1) view of DNA
methylation in the same samples as shown in (A). Compared to the other genomes,
extraembryonic DNA showed a unique pattern of global hypomethylation
interspersed among megabase domains of deeper hypomethylation. Similarly, colon
tumor DNA was hypomethylated, but in a different pattern. (C) As compared to the
other embryonic and fetal samples, 2nd trimester CTBs had an
intermediate level of DNA methylation. At term, the cells acquired higher levels
of methylation similar to the colon tumor. (D–E) Averaged DNA methylation
levels over +/− 15 kb regions of gene bodies (RefSeq) and +/− 3 kb
regions of transposable elements showed the same trends as in (C). 2nd/3rd
trimester CTBs, n=2; 2nd/3rd chorionic villi, smooth chorion, and basal plate,
n=1; tri., trimester; TSS, transcription/transposon start site; TES,
transcription/transposon end site.