a-c, The CpG methylation (a), mRNA
expression levels (b) and DNase signal (c) of
enhancer-interacting and skipped promoters in tissues where enhancers are
active. High me, high methylation skipped promoters (>50% CpG
methylation within ± 1 kb from TSS). Low me, low methylation skipped
promoters (<50% CpG methylation within ± 1 kb from TSS).
d,e, H3K27me3 (d), H3K9me3
(e) signal at ± 2.5 kb of enhancer-interacting and
skipped promoters in tissues where enhancers are active. The pie charts
below show the fraction of promoters marked with H3K27me3 or H3K9me3.
f, Pie charts showing the fraction of skipped promoters
marked by CpG methylation, H3K27me3, H3K9me3 or the combination of marks.
g-i, Violin plot showing CpG length
(g), or CpG methylation level at transcription start sites
for enhancer-interacting and skipped genes with different window sizes
± 250bp (h) and ± 2kb (i)). The
number of high and low methylated skipped as well as interacting promoters
in CpG analysis are n =58, n =86 and
n =71 (CF), n =138, n
=126 and n =90 (FB), n =64,
n =116 and n =96 (FL) and
n =100, n =162 and n
=102 (HB), n =55, n =92 and
n =91 (HL), n =213, n
=169 and n =125 (MB) and, n =87,
n =86 and n =87 (NT). FB, forebrain.
MB, midbrain. HB, hindbrain. CF, craniofacial mesenchyme. FL, forelimb. HL,
hindlimb. NT, neural tube. HR, heart. P values are
calculated by two-sided Wilcoxon rank test after adjusted for multiple
testing (a-c, f-i) or by one-sided chi-squared test (d, e). A statistical
test was not performed for H3K9me3 since most of the values are zero. The
same DNA methylation, mRNA expression, DNaseI hypersensitivity, H3K27ac and
H3K9me3 dataset (a mixture of fore- and hindlimb buds) were used for both
fore- and hindlimb interaction analyses. For the boxplots in panels a-e and
g-i, the central horizontal lines are the median, with the boxes extending
from the 25th to the 75th percentiles. The whiskers further extend by
±1.5 times the interquartile range from the limits of each box.