Supplementary Fig.S1. MeDIP RPKM distribution of 5kb windows. Relative expression of DNMT. Percentage of genome. (fold change)

Transcription

1 Supplementary Fig.S1 Percentage of genome 10% 8% 6% 4% 2% 0 MeDIP RPKM distribution of 5kb windows >1 MeDIP RPKM value EC Relative expression of DNMT (fold change) EC DNMT1 DNMT2 DNMT3 DNMT3 C D DNMT1 mrn expression : RPKM G1 G2 G3 G1 G2 G3 EC-MSI-H EC-MSS -MSS DNMT3 mrn expression : RPKM G1 G2 G3 G1 G2 G3 EC-MSI-H EC-MSS -MSS DNMT3 mrn expression : RPKM G1 G2 G3 G1 G2 G3 EC-MSI-H EC-MSS -MSS Relative expression of XIST (fold change) EC

2 Supplementary Fig.S2 DMRs overlap ENCODE open chromatin features Percentage 80% 60% 40% 20% Hypomethylated Hypermethylated 8 Hypomethylated Hypermethylated TFS TFS DHS DHS 6 Enrichment EC EC 0 EC EC 50% 40% Hypermethylated EC EC-Shared Genomic distribution of DMRs 60% 50% Hypomethylated Percentage % 20% 10% 40% % 20% 10% 0 Intergenic CpG Island Promoter 5 UTR Exon Intron 3 UTR Enhancer 0 Intergenic CpG Island Promoter 5 UTR Exon Intron 3 UTR Enhancer C D E EC-3 EC-2 EC % 100% 80% 60% 40% 20% With Infinium probe Without Infinium probe 80% 60% 40% 20% EC-MSI-H, Grade3 -MSS, Grade3 0% Shared-DMRs EC tpdmrs tpdmrs 0% Shared DMRs EC tpdmrs tpdmrs MeDIP-seq RPKM 8

3 Supplementary Fig.S3 GO Molecular Function Transcription regulatory region sequence-specific DN binding Neurotransmitter transporter activity Core promoter proximal region DN binding GO iological Process Regionalization Neuron fate commitment Cell differentiation in spinal cord nterior/posterior pattern specification GO iological Process Cell fate specification Forelimb morphogenesis Regulation of cell development Regulation of neuron differentiation log10(p-value) EC tpdmr tpdmr Hypermethylated promoter in EC Cell-cell adhesion Cell-cell signaling Transcription factor activity Second-messenger-mediated signaling Ion channel complex Regulation of cmp biosynthetic process Endocrine system development Glutamate receptor activity Regulation of response to external stimulus Morphogenesis of an epithelium Embryonic morphogenesis Hypomethylated promoter in EC Serine protease Hypermethylated promoter in Cell-cell adhesion Chromatin assembly log10(p-value)

4 Supplementary Fig.S4 Expression: log2(rpkm) MRVI RHGP ZT OPCML CDM PRKCDP MEG3 % LDH CDH IRF8 p < 1e-5 p < 1e-2 ^ p < 0.05 EC(MSI-H,Grade3) EC(MSS,Grade3) (MSS,Grade3) DKK1 MRVI1 RHGP20 ZT16 THY1 OPCML PX6 CDM3 PRKCDP PHOX2 PHLD3 SLC58 SCL1 TX5 MEG3 JDP2 ONECUT1 LDH12 CDH13 IRF8 PPP1R1 DCC MeDIP-seq DMRs EC-1 EC-2 EC N-Endo EC-1 EC-2 EC RepeatMasker RefSeq genes 5 end 2kb 3 end 2kb 1kb around TSS Hypermethylated DMR Hypomethylated DMR

5 Supplementary Fig.S5 Expression: log2(rpkm) EP41L PEG THD ^ CDH4 ^ TMEFF2 ^ TWIST LSMP MLH PLCD FT PCDH KP D2IP UHRF RPS6K6 MeDIP-seq DMRs EC-1 EC-2 EC N-Endo EC-1 EC-2 EC RepeatMasker RefSeq genes p < 1e-5 p < 1e-2 ^ p < 0.05 EP41L3 GLR1 EC(MSI-H,Grade3) EC(MSS,Grade3) (MSS,Grade3) PEG3 THD CDH4 TMEFF2 TWIST2 SOX11 LSMP MLH1 PLCD1 LTF RSSF1 FT4 PCDH10 IRX1 KP12 CNTNP2 D2IP UHRF2 RPS6K6 5 end 2kb 3 end 2kb 1kb around TSS Hypermethylated DMR Hypomethylated DMR C Methylation level of MLH1 promoter DN methylation Grade3 EC(MSI-H) EC(MSS) (MSS)

6 Supplementary Fig.S6-3kb CDH1 TSS EC(MSS,Grade3) (MSS,Grade3)+3kb SFN CDH1 SFN EC mrn expression: log2(rpkm) mrn expression: log2(rpkm) CGI Refseq genes 450K probe C controls p < 1e-5 p < 1e-2 EC(MSI-H,Grade3) DN methylation p < 1e-8 p < 1e-3 EC(MSI-H, Grade3) controls cg cg cg cg cg cg cg cg cg cg

7 Supplementary Fig.S7 MeDIP and MRE RPKM fold change on chromosome 10 at 500kb resolution Global DN methylation change (normalized, log2) MeDIP-seq MRE-seq Chr10 ized MRE-seq of normal endometrium ized MeDIP-seq of normal endometrium EC EC

8 Supplementary Fig.S8 MiRN-cluster lncrn EC Hypermethylated 24 9 Hypomethyalted 6 2 Hypermethylated Hypomethyalted mirn expression: log2(rpm) MIR200 MIR200 MIR200C MI653 MIR429 MSI-H EC MSS EC MSS mirn expression: log2(rpm) C MSI-H EC MSS EC MSS MIR542 MIR23 E MIR1247 MIR195 MIR27 MIR497 MIR192-2 MIR450-1 MIR MIR141 MIR MIR74 MIR9-3 MIR93 MIR99 MIR324 MIR106 MSI-H EC MSS EC MSS mirn expression: log2(rpm) D EC CGI RefGene MIR200 MIR200 MIR429

9 Supplementary Fig.S9 EC CGI RefGene MEG3 RN expression: RPKM MEG3 p < 0.05 p < 0.05 p < 0.05 EC-MSI-H EC-MSS -MSS

10 Supplementary Fig.S10 Methylation pattern MMU: EC DMR with promoter state Disease Ontology & Mouse Phenotype : -log10(p-value) abnormal trophoblast giant cells abnormal pancreatic alpha cell physiology abnormal cervical atlas morphology decreased white adipose tissue amount decreased hematocrit abnormal white adipose tissue amount slow postnatal weight gain decreased fetal size delayed suture closure decreased placenta weight anemia Methylation pattern UMU: EC DMR with promoter state GO iological Process: -log10(p-value) odontogenesis of dentine-containing tooth skeletal system development embryonic organ morphogenesis embryonic morphogenesis embryonic skeletal system development giant cell tumor of bone Methylation pattern UUM: DMR with promoter state GO Molecular Function: -log10(p-value) Methylation pattern UUM: EC DMR with promoter state GO Molecular Function: -log10(p-value) nucleic acid binding cell differentiation in spinal cord DN binding neuron fate commitment sequence-specific DN binding embryonic morphogenesis nucleic acid binding transcription factor activity DN-dependent cell fate positive regulation of transcription regionalization DCY3 p < 1e-4 p < 1e-7 p < 1e-7 organ morphogenesis pattern specification process RN expression: RPKM EC-MSI-H EC-MSS -MSS

11 Supplementary Fig.S11 DN methylation change of transposable element families L1 L2 LTR MIR SINE Fold change EC EC EC EC EC EC EC EC EC EC MeDIP MRE MeDIP MRE MeDIP MRE MeDIP MRE MeDIP MRE Fold change lu EC EC ERV EC EC ERV1 EC EC ERVK EC EC ERVL EC EC MeDIP MRE MeDIP MRE MeDIP MRE MeDIP MRE MeDIP MRE

12 Supplementary Fig.S MRE-seq -3 EC-1 EC-2 EC MeDIP-seq -3 EC-1 EC-2 EC-3 LTR6 (136 copies) MER52 (1413 copies) Hypomethylated Hypermethylated Δ RPKM: