SupplementaryTableS3

Top10molecularandcellularfunctionsofbivalentgenes,whichbecomeactivatedincolontumors. Geneswithactivationofatleasttwofoldintumorsandcorrespondingtobivalentstatusinmucosa wereanalyzed(www.ingenuity.com).

Genesymbol pvalue

ST6GAL1,BMP4,F2R,SUV39H1,MKI67,MAPK13,CCND1,OCLN,TESC,MFAP2,EPHB1,PTPRO,MYB,DIAPH2,CSTF2,RNF128,PRDM1,F OSL1,PTF1A,ITGB4,APEX2,ICOSLG,FGF19,CR2,SFRP4,PPP1R1B,ITGA6,RRM2,PTPN3,MET,CCNO,CDH1,PRPS2,NRCAM,SNAI2,FSC

N1,SYK,IFNLR1,DACH1,HPRT1,DUSP4,MEST,STEAP3,SIGIRR,AATF,PHLDA2,PRDX4,DKC1,CTHRC1,PROX1,BCL11B,CDX1,LAMP3,V CAN,ELF4,CDCA7,F2RL1,TFAP2A,PRRX1,ABCB7,CD24,ACSL4,LY75,LIPG,BTG4,BCAP31,AMOT,GJB2,TACSTD2,IGF2BP3,TGFBI,TBX 3,MAP7,CASK,F11R,DGKZ,FA2H,DHCR24,LYN,HOXB9,IHH,FBP1,PAX6,CBX4,PTGS2,PLAU,ABCC3,HRASLS,CYP2S1,LIF,CDCP1,EPH B2,TP73,SLC29A2,UNC5B,PTHLH,IGBP1,TRPC3,PBK,TCF7,WRN,GRB7,SIM2,MYBL2,PRLR,SH3KBP1,ELOVL7,DSP,PGK1,GCH1,GLA

1.54E-12 ,COL4A1,MYH14,CABLES1,ACSL6,CDX2,BCL2L10,BAMBI,FOXC1,HAS3,MECOM,PPP1R13L,ADAM12,FERMT1,GAD1,FOXA2,LAM Proliferation A3,EPCAM,LFNG,IRF8,HIST1H2BH/HIST1H2BO,BUB3,RBP4,MDFI,TEAD4,LITAF,SIX4,HOXD13,TNFRSF12A,IRAK1,SOX9,SIX1,ARN

Cellular Growth and TL2,GALNT3,EFNB1,GATA6,LRRC26,GNG4,E2F8,IRF4,UHRF1,CXCR4,G6PD,IKBKE,ERBB3,TNFRSF11A,HUNK,PIGA,SERPINE2,MST 4,COL1A1,PTPRU,VAV3,LAS1L,UBA1,ASCL2,PPAP2C,DLL4,NRARP,SHMT2,PIM2

ST6GAL1,TPBG,BMP4,F2R,CCND1,OCLN,SATB2,EPHB1,PTPRO,MYB,DIAPH2,FOSL1,PRDM1,ITGB4,MYO5B,ICOSLG,FGF19,CR2,SF RP4,RRM2,ITGA6,MET,CDH1,IL17RB,NRCAM,SYK,FSCN1,SNAI2,ST14,VSNL1,PROX1,BCL11B,CDX1,VCAN,GLRB,ELF4,CHDH,F2RL 1,TFAP2A,CMTM8,ACSL4,CD24,AMOT,GJB2,NMU,TACSTD2,TGFBI,TBX3,RAP2C,F11R,ANXA3,LYN,PAX6,HOXB9,PLAU,PTGS2,CY P2S1,REPS2,LIF,EPHB2,CDCP1,TP73,UNC5B,PTHLH,IGBP1,PLA2G7,PBK,GRB7,SIM2,IRX2,PRLR,FXYD5,MYO10,SH3KBP1,COL4A1, CDX2,SYT7,FOXC1,HAS3,ADAM12,FERMT1,ETV4,FOXA2,GAD1,LAMA3,EPCAM,IRF8,TMEM176B,LITAF,SIX4,CFTR,DCDC2,CLCN4

1.17E-09 ,TNFRSF12A,MFI2,SIX1,EFNB1,GATA6,ACP5,CXCR4,G6PD,ERBB3,TNFRSF11A,SERPINE2,COL1A1,PTPRU,CLDN1,VAV3,MNX1,DLL 4 Cellular Movement

BMP4,F2R,CCND1,OCLN,EPHB1,PLS3,PTPRO,MYB,DIAPH2,RNF128,PRDM1,FOSL1,ITGB4,CR2,ITGA6,MET,CDH1,NRCAM,SLC26A 4,SNAI2,SYK,ITPR3,ST14,STEAP3,SIGIRR,DKC1,PROX1,KREMEN1,BCL11B,KCNQ1,PROM1,VCAN,ELF4,CMTM8,PRRX1,LY75,AMO T,TGFBI,COL12A1,RAP2C,YBX2,F11R,FA2H,LYN,PAX6,IHH,CBX4,PLAU,GALNT6,LIF,EPHB2,TP73,CDCP1,PTHLH,IGBP1,TRPC3,AM

Cell PH,MYBL2,PRLR,MYO10,GLA,COL4A1,CDX2,HOXB8,HAS3,MECOM,PPP1R13L,ADAM12,FERMT1,GAD1,LAMA3,LFNG,IRF8,TME

1.85E-08 M176B,RBP4,HMGB3,TEAD4,CFTR,IRAK1,SIX1,SOX9,EFNB1,GALNT3,ACP5,GRIN2B,IRF4,CXCR4,G6PD,ERBB3,UGT8,TNFRSF11A, Morphology PIGA,SERPINE2,COL1A1,CLDN1,VAV3,MNX1,PIM2

NKD1,BMP4,F2R,SUV39H1,MAPK13,MKI67,DIO2,CCND1,TESC,SATB2,PTPRO,MYB,RNF128,CSTF2,FOSL1,PRDM1,PTF1A,ITGB4,I COSLG,CR2,FGF19,EFNA2,SFRP4,FFAR4,PPP1R1B,ITGA6,RRM2,MET,PRPS2,CDH1,NRCAM,SYK,FSCN1,SNAI2,DACH1,DUSP4,ST1 4,STEAP3,AATF,CTHRC1,PROX1,BCL11B,ALX1,CDX1,VCAN,ELF4,TFAP2A,F2RL1,CMTM8,ABCB7,PRRX1,ACSL4,CD24,BTG4,AMOT ,TACSTD2,IGF2BP3,TBX3,MAP7,TRIB3,CASK,F11R,DGKZ,FA2H,LYN,PAX6,IHH,HOXB9,CBX4,PLAU,PTGS2,HRASLS,LIF,SLC9A3,TP7 3,CDCP1,UNC5B,PTHLH,IGBP1,PBK,TCF7,WRN,GRB7,SIM2,DKK2,MYBL2,PRLR,DSP,ELOVL7,GCH1,COL4A1,ESRP1,HIST1H4A (includesothers),SABLES1,MYH14,ACSL6,CDX2,BAMBI,FOXC1,HAS3,MLPH,MECOM,EBP,PPP1R13L,FERMT1,ETV4,FOXA2, 7.52E08 LAMA3,EPCAM,LFNG,IRF8,HMGB3,TEAD4,MDFI,SCD,LITAF,NLGN1,IL20RA,GABRB2,TNFRSF12A,SOX9,SIX1,GALNT3,EFNB1,GAT A6,LRRC26,TFCP2L1,GNG4,E2F8,IRF4,UHRF1,CXCR4,G6PD,UGT8,ERBB3,IKBKE,HUNK,TNFRSF11A,PIGA,SERPINE2,MST4,COL1A Cellular Development 1,PTPRU,VAV3,MNX1,PITX1,LAS1L,ADRA2C,ASCL2,UBA1,PPAP2C,DLL4,NRARP,PIM2 ST6GAL1,BMP4,F2R,TMEM132A,MKI67,MAPK13,CCND1,OCLN,TMEM102,PTPRO,MYB,PRDM1,FOSL1,ITGB4,ICOSLG,FGF19,CR 2,EFNA2,SFRP4,KCNH8,PPP1R1B,RRM2,ITGA6,MET,CDH1,IL17RB,NRCAM,SLC26A4,SYK,SNAI2,ITPR3,DACH1,HPRT1,DUSP4,CER KL,VSNL1,ST14,STEAP3,SIGIRR,HSD17B10,AATF,PHLDA2,PRDX4,DKC1,KCNQ1,BCL11B,CDX1,VCAN,ELF4,TFAP2A,F2RL1,ABCB7, CD24,ACSL4,BCAP31,AMOT,GJB2,CELSR1,TGFBI,TBX3,TRIB3,CASK,YBX2,FA2H,DHCR24,LYN,PAX6,IHH,HOXB9,CBX4,PTGS2,PLA U,ABCC3,HRASLS,REPS2,LIF,TP73,EPHB2,CDCP1,SLC29A2,PTHLH,UNC5B,IGBP1,PBK,PLA2G7,TCF7,WRN,GRB7,SIM2,MYBL2,PRL R,SH3KBP1,DSP,GCH1,COL4A1,CABLES1,CDX2,BAMBI,BCL2L10,FOXC1,MECOM,PPP1R13L,ADAM12,FOXA2,NUP210,ULBP3,LA

3.59E07 MA3,IRF8,RBP4,GAS2,SCD,SIX4,LGR5,CFTR,SLC25A5,CLCN4,IRAK1,TNFRSF12A,GABRB2,SIX1,SOX9,EFNB1,GALNT3,GATA6,E2F8, DNASE1L1,GRIN2B,IRF4,UHRF1,CXCR4,RTKN,G6PD,IKBKE,ERBB3,UGT8,TNFRSF11A,PIGA,SPINT1,MST4,SERPINE2,COL1A1,AK5, VAV3,UBA1,DLL4,PIM2

Cell Death and Survival Lipid Cell-To-Cell Molecular Gene Cellular Metabolism Signaling and Transport Expression Function and Interaction Maintenance

9.48E05 9.50E06 9.02E06 2.31E06 1.60E06 RINC2,EBP,DHCR24,GA ,SYK,LAMA3,LYN,EPCAM,PLAU,VSNL1 YP2S1 B3,IKBKE,OVOL1,CASK,YBX2,COL1A1,VAV3,MNX1,PITX1,NKRF,LYN,IGF2 ,ALX1,ZBTB33,CDX1,IRAK1,ELF4,SIX1,SOX9,F2RL1,ARNTL2,TFAP2A, 1R13L,SYK,SNAI2,FOXA2,ETV4,DACH1,DUSP4,IRF8,HMGB3,MDFI,TEAD4,LITAF,EVX1,AATF,SIX4,HOXD13,PROX1,KCNQ1,BCL11B OSL1,MYBL2,PTF1A,PRLR,HIST1H1B,SH3KBP1,CR2,NFE2L3,SFRP4,PP LIF,BMP4,F2R,TP73,SUV39H1,IGBP1,CCND1,TCF7,TESC,SATB2,EPHB1,WRN,AM 4,SLC9A7,F2RL1,ABCB7,EFNB1,CD24, A2,SYK,SNAI2,DACH1,LAMA3,LFNG,IRF8,ATP2C2,RBP4,SIGIRR,SCD,AATF,NLGN1,CFTR,B DSC2,SH3KBP1,DSP,ICOSLG,SFRP4,PLEKHA7,COL4A1,ICA1,PKP2,PPP1R1B,MECOM,MET,CDH1,NRCAM,SLC25A14,SLC26A4,FOX LIF,BMP4,RIMS2,F2R,TP73,SLC9A3,EPHB2,PTHLH,MAPK13,TRPC3,CCND1,TCF7,TESC,OCLN,EPHB1,MYB,RNF128,PRDM1,ITGB4, 2L1,PHKA1,SH3KBP1,PNPLA4,ELOVL7,FGF19,NSDHL,GLA,ACSL6,ITGA6,G6PD,MAP7,DGAT2,SLC35A2,TRIB3,UGT8,SERPINE2,SE SIGIRR,SCD,LIF,BMP4,SLC27A2,PROX1,CFTR,PLA2G7,MOGAT1,TNFRSF12A,F2RL1,CDS1,MID1IP1,GATA6,ACSL4,LIPG,PRLR,TFCP ,CR2,COL4A1,PLEKHA7,TGFBI,PKP2,CXCR4,ITGA6,ERBB3,HAS3,MECOM,MET,COL1A1,CAMSAP3,CDH1,ADAM12,NRCAM,CLDN1 MATN3,ST6GAL1,LIF,F2R,CDCP1,NLGN1,EPHB2,CCND1,TRPC3,VCAN,OCLN,EPHB1,EFNB1,CD24,MYBL2,FXYD5,AMOT,GJB2,DSP BRB1,MYB,PRLR,GABR SCD,F2R,EPHB2,SLC9A3,SLC4A11,SLC29A2,PTHLH,CFTR,KCNQ1,SLC25A5,TRPC3,CLCN4,GABRB2,IRAK1,GLRB,SLC9A7,F2RL1,GA DGKZ,CLDN1,VAV3,MNX1,LYN,PAX6,IHH,PLAU, E,BCAP31,SH3KBP1,SFRP4 D1,SYK,LYN,PTGS2,PLAU,HRASLS BCAP31,AMOT,GJB2,NMU,CLIC5,GRIN2B,IRF4,TBX3,CXCR4,TRIB3,TNFRSF11A,CAMSAP3, PTGS2,ABCC3,DLL4,NRARP,PIM2 ,GRIN2B,CLIC5,CXCR4,CLCN5,DGKZ,SLC26A4,SYK,LYN,ABCC3,ATP2C2 PRRX1,GATA6,TFCP2L1,TOX3,IGF2BP3,IRF4,TBX3,CXCR4,TRI P1R1B,CDX2,BAMBI,FOXC1,HAS3,MECOM,MET,CDH1,PPP BP2,PAX6,IHH,HOXB9,CBX4,ASCL2,DLL4,NRARP,PIM2,C PH,GRB7,MYB,SIM2,MID1IP1, CL11B,KCNQ1,IRAK1,GABRB2,GLRB,ELF DIAPH2,PRDM1,F