PCR amplification was performed on bisulphite-treated DNA samples with the
primers covering the paternally inherited imprinting control region of two
imprinted regions (Figure
S2). Then the PCR product was subjected to restriction enzyme
digestion targeting the CpG sites. uES, undifferentiated ES cell samples derived
from the ES cells grown on feeder cells. dES, differentiated ES cell samples
derived from the ES cells passaged on gelatin-coated plates for two generations.
EB, embryoid bodies formed after the ES cells grown on non-adherent 10-cm dish
plates for 9 days. Lanes 1, wild-type (WT) ES clone. Lanes 2, TET DKO#1
ES clone. Lanes 3, TET DKO#2 ES clone. Lanes 4, TET TKO#1 ES
clone. Lanes 5, TET TKO#2 ES clone. u, the restriction enzyme product of
the unmethylated DNA. m, the restriction enzyme product of the methylated
DNA.
A, COBRA analysis of the H19 DMR of the
Igf2-H19 imprinted region, with a PCR product of 461 bp
(Figure S2A).
ClaI, RsaI, BstUI and
TaqαI are four restriction enzymes used
for digestion. The sizes of the restriction enzyme digestion product for the
methylated DNA are: 350 bp and 111 bp for ClaI; 340 bp and 121
bp for RsaI; 379 bp and 82 bp for BstUI; 349
bp and 112 bp for TaqαI. B, COBRA analysis
of the IG-DMR of the Dlk1-Dio3 imprinted region, with a PCR
product of 384 bp (Figure
S2B). HpyCH4IV and
TaqαI are two restriction enzymes used
for digestion. The sizes of the restriction enzyme digestion product for the
methylated DNA are: 280 bp and 104 bp for ClaI; 267 bp and 117
bp for TaqαI.