Supplementary material 1

250 211 200

150 120 122

100

50 15 0 Biased Forward- Reverse- Any orientation reverse (FR) forward (RF) orientation (FR+RF) Supplemental Figure S1. Biased-orientations of DNA motif sequences of factors in

T cells. Total 211 of biased orientations of DNA binding motif sequences of transcription factors were found to affect the expression level of putative transcriptional target in T cells of four people in common, whereas only 15 any orientation (i.e. without considering orientation) of

DNA binding motif sequences were found to affect the expression level.

1 ) ) )

* * * HiChIP HiChIP HiChIP 0.7 CTCF * 0.7 RAD21 * 0.7 SMC3 * 0.6 0.6 0.6 0.5 0.5 0.5 0.4 0.4 0.4 0.3 0.3 0.3 0.2 0.2 0.2 0.1 0.1 0.1 0 0 0 others any FR FR others any FR FR others any FR FR H3K27ac H3K27ac H3K27ac Ratio of EPI overlapped with interactions ( Ratio of EPI overlapped with interactions ( chromatin Ratio of EPI overlapped with interactions ( chromatin ) ) ) * * * 1 1 1 HiChIP CTCF * HiChIP RAD21 * HiChIP SMC3 * 0.8 0.8 0.8 0.6 0.6 0.6 0.4 0.4 0.4 0.2 0.2 0.2 0 0 0 others any FR FR others any FR FR others any FR FR H3K27ac H3K27ac H3K27ac Ratio of EPI overlapped with interactions ( chromatin Ratio of EPI overlapped with interactions ( chromatin Ratio of EPI overlapped with interactions ( chromatin Supplemental Figure S2. Comparison of enhancer-promoter interactions (EPI) with chromatin interactions in T cells. EPI were predicted based on enhancer-promoter association (EPA) shortened at the genomic locations of biased orientations of DNA binding motif sequence of a . Total 51 biased orientation (33 FR and 23 RF) of DNA motif sequences including CTCF and cohesin showed a significantly higher ratio of EPI overlapped with three replications of HiChIP chromatin interactions respectively than the other types of EPAs in T cells. The upper part of the figure is a comparison of EPI with HiChIP chromatin interactions with more than 6,000 counts for each interaction, and the lower part of the figure is a comparison of EPI with HiChIP chromatin interactions with more than 1,000 counts for each interaction. FR: forward-reverse orientation of DNA motif. any: any orientation (i.e. without considering orientation) of DNA motif. others: enhancer-promoter association not shortened at the genomic locations of DNA motif. FR H3K27ac: EPI were predicted using DNA motif in open chromatin regions overlapped with H3K27ac histone modification marks. * p-value < 10-2.

2 Supplemental Table S1. Forward-reverse and reverse-forward orientations of DNA binding motif sequences of transcription factors in monocytes of four people

Forward-reverse orientation

TF Score TF Score TF Score TF Score TF Score TCF3 123.12 ETS 49.44 DDIT3 29.23 HMGA1 20.98 BCL6 8.47 ZNF592 120.55 SOX6 49.42 NRF1 28.86 TCF12 20.85 PRRX2 8.30 EOMES 109.78 AP2A 49.36 SREBP2 28.63 MGA 20.57 ZNF22 7.06 GMEB2 75.32 CEBPA 47.31 YY1 28.02 TBX15 20.57 MAFG 6.77 CEBPG 74.27 FOSL1 44.41 FOXM1 27.64 DNTTIP1 20.39 ZEB1 5.96 FOXA1 73.14 ATOH1 43.94 VSX1 27.38 SOX30 19.66 PEA3 5.85 FOXA2 72.93 NFATC2 43.63 AP-1 27.13 CEBPB 18.90 ETV4 5.85 DBX2 72.66 TBX3 42.82 STAT5A 26.61 CDX2 17.84 RXRA 5.71 NFYA 71.62 CREB 42.45 KLF10 26.24 YY2 17.58 EHF 3.31 TP53 66.60 EGR1 41.57 mix-a 26.06 EGR4 17.51 POU1F1 3.27 65.71 HOXA4 41.47 HLF 25.64 JUN 17.35 TLX2 64.10 FOXO1 40.92 FOXG1 25.44 RXR 17.13 IKZF1 63.69 BARHL1 40.43 DLX3 24.92 IRF3 16.77 RFX6 61.62 ZNF189 39.78 ZNF180 24.86 NFIC 16.59 SFN 59.89 SP1 39.54 BARX2 24.45 NFE2L1 16.44 FOXO3 59.78 ATF3 37.30 REST 24.25 BHLHE40 16.19 ZBTB18 59.45 CTNNB1 37.01 SMAD 24.05 SALL4 15.27 PPARG 57.25 ZNF579 36.10 RAD21 23.98 RFX1 14.26 ZNF675 54.71 MZF1 35.58 SRY 23.97 USF1 12.95 HNF1B 53.86 BACH2 35.38 LRF 23.46 HOXA2 12.23 ITGB2 53.86 ZIC1 34.59 ZNF300 22.62 NFATC1 12.16 RFX4 53.41 CTCFL 34.55 FOXJ2 22.35 SOX10 12.08 TBP 53.06 CXXC1 34.42 TCF7 22.18 EGR2 12.06 CBFB 52.31 GCM2 34.26 MNX1 21.99 ELF5 10.58 TEAD1 51.39 MEIS1:EOMES 34.02 SOX 21.98 HMGN3 10.14 ZBTB7A 50.61 HNF4 34.00 MAZ 21.87 HMX1 9.83 CTCF 50.54 HINFP 33.29 HMGIY 21.53 DLX5 9.69 SOX5 50.51 PDX1 32.36 STAT4 21.33 9.38 BRCA1 50.47 CEBPD 30.87 TBR1 21.22 MAFB 8.80 SOX3 49.47 RUNX1 29.40 NKX2-5 21.17 8.52 Reverse-forward orientation

TF Score TF Score TF Score TF Score TF Score ZBTB48 175.35 HOXA11 47.37 CEBP 32.34 ETS2 19.33 MEOX1 9.75 ZBTB38 107.55 POU4F3 46.76 RUNX3 32.09 GATA3 19.30 TCF12 8.65 MSX1 105.86 LBX1 46.13 TCF7 31.09 ATF3 18.86 GTF2B 8.58 POLYA 98.31 NR5A1 44.93 AR 30.08 TBX5 18.30 ASCL2 6.96 RFX5 97.45 ETV5 44.91 ZBTB7B 29.59 BCL3 17.51 MBD2 6.21 SMAD1 83.39 FOXL1 44.50 ESX1 29.45 SPI1 16.98 STAT5A 5.98 YBX1 80.34 NFATC2 43.63 CTNNB1 29.43 ETS1 16.71 CPBP 4.39 79.72 NR3C1 42.45 HDAC2 29.27 MITF 16.59 JUNB:JUN 4.34 NR2C2 78.27 ETV6 41.44 HIC1 29.16 AP-1 16.55 OTX 74.43 TFAP2A 40.97 NRF1 29.02 CAR_RXR 15.93 CEBPG 74.27 TCF7L2 40.86 HOXD3 28.50 NFATC3 15.76 SP1 73.86 PGR 40.58 ZFP42 28.20 FOSL1 15.72 BARHL1 72.65 SP2 39.15 NR4A1 27.71 IRF8 14.61 PITX3 71.71 EBF1 38.13 NR4A3 25.50 NKX6-1 14.52 TEAD3 68.36 ZNF384 37.81 LMX1A 25.31 USF2 14.45 FOXA2 68.31 ISX 37.47 NFATC4 25.26 FOXJ2 14.07 ZBTB16 68.09 GFI1 36.99 PAX2 25.04 MEOX2 12.91 EN2 64.71 ATF6 36.81 RAX2 24.73 BCL 12.85 HOXA7 64.52 REST 36.52 FOXD2 24.55 GEN_INI 12.53 ZBTB7A 63.80 NFYB 36.38 RHOXF1 23.71 FOXM1 12.28 NFATC1 61.71 FOS 36.12 CTCFL 23.46 POU5F1 12.27 KLF2 61.64 RUNX2 35.21 CREB1 23.28 EMX1 12.23 TEAD1 61.03 YY1 34.76 EN1 22.00 KLF16 12.10 STAT 56.11 CREB3 34.64 SPIB 21.81 FOXI1 11.94 SOX6 55.25 MEIS1 34.49 NFAT 20.97 MEIS3 11.92 TFAP2C 53.06 CTCF 33.99 LEF1 20.94 PAX8 11.60 HOXA2 52.05 EGR1 33.22 MYB 20.77 NFIC 11.46 FOXO4 51.30 ISL2 33.21 NKX3-2 20.72 SPIC 11.03 ZBTB18 49.30 RUNX1 33.17 CCAAT 20.42 PITX1 10.63 SPDEF 49.26 PDX1 32.57 FLI1 19.65 PRDM1 10.30

3 Supplemental Table S2. Forward-reverse and reverse-forward orientations of DNA binding motif sequences of transcription factors in T cells of four people

Forward-reverse orientation

TF Score TF Score TF Score TF Score USF1 140.57 CTCFL 46.54 STAT1 27.55 TFE 14.39 RFX7 120.15 TBX5 45.72 EP300 27.54 KLF7 14.11 BPTF 109.36 RAD21 45.68 NKX3-2 27.50 MAZ 14.01 FOXL1 103.21 RUNX1 44.69 KLF1 26.57 TEAD1 13.95 GATA3 99.78 RUNX2 44.50 AR 25.48 PRDM16 13.92 NKX2-2 84.09 AP-1 44.37 FOXM1 25.32 PURA 12.86 ZIC1 83.63 E2F6 43.27 IRF4 25.14 ZXDC 12.49 SREBF2 82.98 ELF1 43.20 ESRRA 24.72 HOXA11 11.67 CTCF 80.45 FOSB 42.80 STAT 24.62 VDR:RXRA 11.00 MYC 77.22 DBP 41.83 HIF1A 23.55 NR2F1 11.00 ZNF263 68.13 TCF3 40.54 HOXB4 22.50 KLF4 10.76 AP2A 65.79 JUNB 40.41 MAF 21.82 YY1 10.66 SOX5 64.97 MZF1 40.21 KLF5 21.74 POU2F2 10.27 HMGA1 58.51 ZBTB7A 39.80 TCF4 21.69 JUN:FOSL1 10.03 SPI1 58.49 E2F 37.83 SP1 21.11 ETV5 9.84 SRY 58.05 ZEB 36.79 VAX2 21.04 EGR1 9.33 SOX9 56.94 NEUROD2 36.35 NFE2L1 20.34 NFE4 9.04 FOXO1 55.17 SOX10 36.33 ZIC3 20.30 MXI1 8.77 BRCA1 54.75 MITF 35.71 KLF10 19.06 BCL 8.26 MSX2 54.09 FOS 34.50 CXXC1 18.99 7.30 SALL4 53.17 IRF 33.62 FOSL1 18.47 HOXD11 7.02 TFAP4 52.97 FOXC1 33.57 NFATC1 17.91 JUND:FOSL2 6.62 NKX2-5 51.98 SMC3 32.00 JUN 17.42 JDP2 6.61 HNF4 50.44 REST 31.66 KLF3 17.20 HSF 6.26 ZNF350 49.64 FOXA1 31.53 NR3C1 16.92 DLX3 5.81 NFIL3 49.39 PAX2 30.37 SMARCC1 16.89 EHF 5.78 CLOCK:ARNTL 49.37 EPAS1 30.32 TEAD4 16.29 HNF4A 5.08 ETS1 47.28 EN1 30.17 NKX2-1 16.22 RBPJ 4.92 ETF 46.69 IKZF1 29.39 LBX1 16.19 YY2 3.56 FOXK1 46.56 ZEB1 28.86 CEBPB 14.97 KLF 3.54 Reverse-forward orientation

TF Score TF Score TF Score TF Score TF Score NR2C2 137.22 RARB 51.96 FOXO3 36.18 PAX5 20.42 AHR 2.34 HDAC1 112.10 JUN:FOSB 51.80 SPIB 36.14 HOXB13 20.31 ZNF250 2.33 FOXJ2:ELF1 112.09 SMAD5 51.10 ELF3 34.68 FOXD3 20.15 IRX2 93.15 SP2 49.89 ZBTB7A 34.58 CRX 19.00 OSR1 90.12 NFIL3 49.39 ZNF572 34.22 HEY2 18.77 GSX1 86.48 HDAC2 49.13 NFIB 32.87 FOSL2 18.53 TFAP2C 84.20 SOX30 48.80 ETV4 32.29 LYL1 18.22 MSX3 84.02 JUNB 48.28 TAF1 32.05 LEF1 18.15 OSR2 81.99 NKX6-1 48.25 FOXP3 32.00 TCF4 17.79 ARID3A 75.98 CEBPA 47.80 YY2 31.63 FOSL1 17.37 PDX1 75.42 FOXL1 46.93 MEQ 31.45 JUND:FOSL1 16.93 BHLHE41 74.42 PAX4 46.84 NFIA+NFIB+NFIC+NFIX 30.03 NFI 15.85 GATA5 74.25 NR4A1 45.78 AP3 29.90 MAZ 15.83 SOX17 72.95 SNAI1 45.35 FOXA2 29.46 HOXB3 15.79 NFKB1 71.45 AP-1 45.31 TBX2 29.34 OVOL 15.68 POU3F2 71.38 ELF5 45.04 SMAD 29.32 HOXB5 14.94 DLX3 70.87 PRRX1 43.47 RUNX1 28.21 IRF1 12.98 PRDM1 68.50 ZNF354C 43.24 TBX5 27.54 FOXB1 12.31 YBX1 68.19 VDR 43.19 IRF7 24.50 EP300 11.88 EHF 68.12 KLF2 42.22 NKX3-2 24.41 SPI1 11.58 SOX4 63.50 CACD 42.06 CREB1 24.31 JUN 10.88 MYOD1 63.47 SOX10 41.14 23.76 HIC2 10.67 BARHL1 62.65 FOS 41.14 PAX8 23.37 JUND:FOS 10.03 SRY 62.09 CTCFL 39.80 RAD21 23.23 JUNB:FOS 9.88 TEF 58.24 SMAD3 39.05 ETS1 23.10 CTCF 9.61 FOXO1 58.05 ETV6 38.97 MEIS1 22.87 NKX2-3 8.52 FOXM1 57.48 LTF 38.81 GATA 21.75 EGR2 6.65 ELF1 56.99 SOX18 38.10 YY1 21.64 JUND 6.60 FOXO4 55.26 SP1 37.66 GATA2 20.94 KLF4 6.54 TCF12 53.82 FOXA1 36.87 PAX3 20.56 KLF8 3.04

4 Supplemental Table S3. Forward-reverse and reverse-forward orientations of DNA binding motif sequences of transcription factors in monocytes of four people using H3K27ac histone modification marks

Forward-reverse orientation

TF Score TF Score TF Score TF Score IKZF1 62.09 HOXA4 30.82 NEUROG2 19.39 STAT5A 11.76 NFYA 61.11 EGR2 30.17 ETS 19.11 YY2 11.35 TCF3 58.71 HMGA1 30.01 SMAD 18.92 SALL4 11.11 ZNF579 53.64 ZGPAT 29.69 STAT4 18.83 NOBOX 10.23 PARP1 48.53 CREB 28.93 CTNNB1 18.75 SRF 10.08 CTCF 45.97 GCM2 28.57 BARX2 18.64 SOX4 9.97 ZBTB7A 42.68 ZIC3 27.89 SOX6 17.87 FOXA2 9.39 EN1 40.59 EGR1 27.79 PHOX2A 17.68 SPIB 8.79 NR0B1 40.58 DLX3 27.59 17.58 ELF5 8.14 BRCA1 39.95 SP1 26.18 JUN 17.11 FOXA 7.82 MZF1 38.01 BHLHE40 26.08 ELK1 16.80 NKX6-3 6.22 ATF3 36.88 mix-a 25.61 16.57 NFE4 6.13 HOXD3 36.40 GATA3 25.43 TEAD1 16.36 RHOX11 5.59 CEBPG 36.28 MAZ 25.35 FOXO1 16.30 ZEB1 5.40 RAD21 36.07 REST 25.26 TBR1 15.68 SMC3 3.73 NKX2-2 35.70 GATAD2A 25.25 ZIC1 15.66 SOX 35.40 CDX2 25.23 TBX1 15.58 CTCFL 35.18 BACH2 24.93 ZBTB7 14.23 SOX3 35.02 WT1 23.08 HMGN3 14.11 TCF7 34.99 TP53 22.36 ISL1 13.97 ZBTB18 34.70 AP-1 22.00 FOXJ2 13.61 EOMES 34.44 ZNF675 21.77 YY1 13.36 NFE2 33.54 ZNF300 21.62 MAFB 13.31 CEBPA 33.31 DDIT3 21.52 FOXA1 12.96 SREBF2 32.80 MYB 21.37 NFIC 12.75 E2F 32.35 E2F4 20.35 CEBPB 12.41 TLX2 32.13 SMAD2 20.00 ELF1 12.37 CBFB 31.89 NR3C1 19.85 USF1 12.13 RFX6 31.54 HOXA2 19.44 MEIS1 12.07 CXXC1 31.42 SOX7 19.42 ZNF189 11.91 Reverse-forward orientation

TF Score TF Score TF Score TF Score ZBTB48 79.26 LEF1 31.47 SPIB 19.83 CEBPB 12.41 HNF4 58.67 Zen 31.21 DLX1 19.54 NRF1 12.12 TEAD3 57.80 NR1I2 30.81 EMX1 19.44 CAR_RXR 11.41 YBX1 56.23 FOXL1 30.62 OTX 19.27 FOXP2 11.18 SP1 56.02 SPDEF 30.06 MEOX2 18.55 AHR 10.74 SOX6 53.00 RORA 29.08 FOXP1 18.14 NFIC 10.53 KLF4 49.37 LMX1A 28.02 CTNNB1 17.66 HOXB2:EOMES 9.29 ZNF740 48.26 GFI1 27.69 TEAD2 17.34 SP3 9.22 TEAD1 46.67 MSX1 27.59 HOXA7 17.16 NKX3-2 8.99 ZNF232 44.34 ZFP42 27.57 HDAC2 16.93 GATA2 8.36 OLIG2 43.68 ZBTB7B 27.31 KLF6 16.68 ARNTL 8.22 ZBTB7A 43.31 HOXA11 27.28 EBF1 16.67 BCL 7.55 BARHL1 42.51 GATA5 27.17 NR4A3 16.23 SMAD5 7.44 EN2 42.36 GRHL2 26.87 KLF2 16.20 NKX2-1 7.09 MEF2D 41.76 PGR 24.91 SP5 15.96 NFYC 6.95 NKX2-5 39.32 FOXD2 24.55 CRX 15.45 EGR1 6.05 ESX1 39.07 ZBTB18 24.44 CREB1 15.32 ERF:DLX3 4.44 NR2C2 38.41 NR3C1 24.37 E2F 15.22 CTCF 37.78 SP2 23.45 STAT5A 14.70 SMAD1 37.34 HOXD9 23.39 CTCFL 14.23 FANK1 37.09 POU4F3 23.36 ETV5 13.81 RFX5 36.98 ATF3 22.91 FLI1 13.69 CEBPG 36.28 FOXA2 22.64 THAP11 13.64 HOXD3 35.98 MYB 22.57 SIN3A 13.60 POU3F1 35.93 ISX 22.31 SOX10 13.39 TCF7L2 34.99 ZBTB16 21.33 CEBPA 13.27 PITX3 33.94 JUNB 21.29 LHX2 13.05 EN1 33.67 AR 20.85 YY1 12.95 PDX1 32.38 LBX1 20.58 HOXA2 12.91 STAT 32.02 PAX2 20.19 NFATC3 12.85

5 Supplemental Table S4. Forward-reverse and reverse-forward orientations of DNA binding motif sequences of transcription factors in T cells of four people using H3K27ac histone modification marks

Forward-reverse orientation

TF Score TF Score TF Score TF Score 87.89 ESRRA 39.63 NR3C1 23.69 LRF 14.38 GATA3 81.24 DBP 39.18 HES1 23.34 BCL 14.35 RFX7 79.49 PAX2 38.84 STAT 23.06 MAZ 12.81 SREBF2 70.97 RAD21 38.80 SOX15 22.61 AFP 10.90 BPTF 60.87 FOXO1A 37.73 VAX1 22.46 MYB 10.03 SPI1 55.64 NKX3-2 37.26 IRF4 22.17 FOXA1 9.87 CTCF 55.25 CLOCK:ARNTL 36.96 ZBTB7A 22.12 MXI1 9.70 AP-1 54.12 USF 35.55 FOXC1 22.01 HOXC10 9.60 SALL4 54.00 ZNF263 35.27 FOXD3 21.66 TFE 9.44 FOSB 51.87 KLF1 34.91 TCF12 21.30 CPEB1 7.77 SOX10 49.75 E2F 34.50 STAT1 21.15 NRF1 7.19 SOX5 49.74 ETS1 34.20 KLF 20.60 AR 5.42 HMGA1 49.63 RUNX1 32.93 ZEB1 20.59 YY2 5.37 JUNB 49.24 SOX17 32.21 TCF4 20.41 EP300 4.49 RUNX2 48.31 RUNX3 30.62 TEAD4 20.28 ISL2 4.35 ZIC1 47.28 ZEB 30.31 ETF 20.17 GTF2I 4.13 FOXO1 45.95 NKX3-1 30.19 BCL6B 19.69 IRF1 3.43 ZNF426 45.58 ZXDB 29.46 TFCP2 19.28 NFY 3.11 SRY 45.25 KLF10 28.86 TCF3 18.88 NKX2-2 45.20 PURA 28.03 SP1 18.33 MZF1 44.53 YY1 27.52 OVOL2 17.51 TFAP4 44.39 SALL2 27.05 IRF 17.15 MSX2 42.78 E2F6 26.90 NKX2-1 16.53 KLF5 42.68 TEAD1 26.08 PRDM16 16.02 BRCA1 42.59 MAF 25.97 TFDP1 15.99 HNF4 42.04 IKZF1 25.68 SMC3 15.35 E2F3 41.91 MITF 25.45 NR2F6 15.25 LEF1 39.97 FOS 25.01 HOXB4 15.19 FOXK1 39.91 MYC 24.42 HMX1 14.94 CTNNB1 39.68 HSF1 23.92 MYOG 14.66 Reverse-forward orientation

TF Score TF Score TF Score TF Score VSX1 106.04 MYB 35.55 NFIC 20.91 NFE2 9.80 NR2C2 97.42 PDX1 35.34 MAFG 20.65 TBX2 9.07 JUNB 68.81 ELF3 34.17 EGR2 18.59 CTCF 7.05 BCL 64.72 ELF5 33.15 FOXP3 18.07 FIGLA 5.26 POU3F2 62.77 POU3F3 32.63 VDR 18.00 LYL1 5.08 PAX4 59.32 RUNX1 32.26 CRX 17.83 PAX5 4.97 ZNF354C 57.04 MEIS1 31.80 SP2 17.62 NR3C1 56.72 YBX1 31.71 ZNF572 17.44 BARHL2 55.72 CEBPA 31.00 IRF7 17.15 AP-1 54.85 SOX18 30.67 ZBTB33 17.00 SOX4 54.01 SP7 29.83 NKX2-2 16.73 TEF 53.64 HDAC2 28.72 FOXB1 16.35 GSX1 53.45 JUN 28.53 E4F1 16.24 SOX10 52.26 ETV4 27.86 SP1 16.11 FOS 50.68 RAD21 27.38 STAT5B 15.21 EHF 50.52 NFKB1 26.96 NR4A1 15.05 ZBTB4 49.84 NKX6-1 26.94 ZBTB14 14.70 FOXO1 48.81 SMAD 26.60 ZBTB7A 14.50 SRY 47.90 JUND:FRA1 26.51 CTCFL 14.38 TAF1 44.78 FOXD3 26.43 SMAD5 14.36 ARID3A 44.67 ASCL2 26.15 NKX3-2 14.08 TFAP2C 44.27 EGR1 25.30 ATOH1 13.94 BHLHE41 42.69 TCF7 23.92 YY2 13.70 FOXM1 40.58 NKX2-8 23.42 EP300 13.07 AP3 40.42 TCF4 23.09 ZBED1 12.87 ELF1 39.92 SOX15 22.61 SNAI2 12.65 CACD 37.26 LEF1 22.52 AR 12.05 TCF12 37.23 MAZ 22.34 HIC1 11.88 35.90 SOX2 21.30 FOXA1 10.16 FOXL1 35.88 PAX3 21.03 GATA 9.83

6 Supplemental Table S5. Biased orientations of DNA binding motif sequences of transcription factors found in both monocytes and T cells. FR: Forward-reverse orientation, RF:

Reverse-forward orientation.

FR and RF (69) FR and RF (69) FR and RF (69) FR (42) FR (42) RF (36) RF (36) AP-1 KLF4 TEAD1 AP-1 SOX10 AP-1 TBX5 AP2A LEF1 TFAP2C AP2A SOX5 BARHL1 TCF12 BARHL1 MAZ USF1 BRCA1 SP1 CREB1 TFAP2C BRCA1 MEIS1 YBX1 CEBPB SRY CTCF YBX1 CEBPB MYC YY1 CTCF TCF3 CTCFL YY1 CREB1 MZF1 YY2 CTCFL TEAD1 ETS1 ZBTB7A CTCF NFATC1 ZBTB7A CXXC1 USF1 ETV6 CTCFL NFE2L1 ZEB1 DLX3 YY1 FOS CXXC1 NKX2-5 ZIC1 E2F YY2 FOSL1 DLX3 NKX3-2 EGR1 ZBTB7A FOXA2 E2F NKX6-1 EHF ZEB1 FOXL1 EGR1 NR2C2 FOSL1 ZIC1 FOXM1 EHF NR4A1 FOXA1 FOXO4 ETS1 PAX8 FOXM1 HDAC2 ETV6 PDX1 FOXO1 KLF2 FOS PRDM1 HMGA1 KLF4 FOSL1 RAD21 HNF4 LEF1 FOXA1 REST IKZF1 MEIS1 FOXA2 RUNX1 JUN NKX3-2 FOXL1 SALL4 KLF10 NKX6-1 FOXM1 SOX10 MAZ NR2C2 FOXO1 SOX5 MYC NR4A1 FOXO4 SP1 MZF1 PAX8 HDAC2 SP2 NFATC1 PDX1 HMGA1 SPI1 NFE2L1 PRDM1 HNF4 SPIB NKX2-5 RUNX1 IKZF1 SRY RAD21 SP1 JUN TBX5 REST SP2 KLF10 TCF12 RUNX1 SPI1 KLF2 TCF3 SALL4 SPIB

FR and RF (88) FR and RF (88) FR and RF (88) AP-1 FOXO3 PRDM1 AP2A FOXO4 RAD21 AR GATA3 REST BARHL1 HDAC2 RUNX1 BCL HMGA1 RUNX2 BRCA1 HNF4 SALL4 CEBPA HOXA11 SMAD CEBPB IKZF1 SOX10 CREB1 JUN SOX30 CTCF KLF10 SOX5 CTCFL KLF2 SP1 CXXC1 KLF4 SP2 DLX3 LBX1 SPI1 E2F LEF1 SPIB EGR1 MAZ SRY EGR2 MEIS1 STAT EHF MITF TBX5 ELF5 MYC TCF12 EN1 MZF1 TCF3 ETS1 NFATC1 TEAD1 ETV4 NFE2L1 TFAP2C ETV5 NKX2-5 USF1 ETV6 NKX3-2 YBX1 FOS NKX6-1 YY1 FOSL1 NR2C2 YY2 FOXA1 NR3C1 ZBTB7A FOXA2 NR4A1 ZEB1 FOXL1 PAX2 ZIC1 FOXM1 PAX8 FOXO1 PDX1

7 Using H3K27ac histone modification marks

FR and RF (45) FR and RF (45) FR (27) RF (23) FR and RF (60) FR and RF (60) AP-1 SALL4 AP-1 AR AP-1 NFIC AR SMAD5 BRCA1 BCL AR NKX2-1 BCL SMC3 CTCF CEBPA BCL NKX2-2 BRCA1 SOX10 CTNNB1 CRX BRCA1 NKX3-2 CEBPA SP1 E2F CTCF CEBPA NR2C2 CRX SP2 FOXA1 CTCFL CRX NR3C1 CTCF SREBF2 FOXO1 EGR1 CTCF NRF1 CTCFL TCF3 GATA3 FOXL1 CTCFL PAX2 CTNNB1 TEAD1 HMGA1 HDAC2 CTNNB1 PDX1 E2F YBX1 IKZF1 JUNB E2F RAD21 EGR1 YY1 MAZ LEF1 EGR1 SALL4 FOXA1 YY2 MYB MYB EGR2 SMAD FOXL1 ZBTB7A MZF1 NFIC ELF1 SMAD5 FOXO1 ZEB1 NKX2-2 NKX3-2 ELF5 SMC3 GATA3 ZIC1 NR3C1 NR2C2 FOXA1 SOX10 HDAC2 RAD21 NR3C1 FOXL1 SOX2 HMGA1 SALL4 PDX1 FOXO1 SOX4 IKZF1 SMC3 SMAD5 GATA3 SP1 JUNB SP1 SOX10 HDAC2 SP2 LEF1 SREBF2 SP1 HMGA1 SREBF2 MAZ TCF3 SP2 HNF4 STAT MYB TEAD1 YBX1 IKZF1 TCF3 MZF1 YY1 ZBTB7A JUN TCF7 NFIC YY2 JUNB TEAD1 NKX2-2 ZBTB7A LEF1 YBX1 NKX3-2 ZEB1 MAZ YY1 NR2C2 ZIC1 MEIS1 YY2 NR3C1 MYB ZBTB7A PDX1 MZF1 ZEB1 RAD21 NFE2 ZIC1

The results of two analyses of biased orientations of DNA motif sequences using open chromatin regions and open chromatin regions overlapped with H3K27ac histone modification marks were merged in each cell type of monocytes and T cells, and biased orientations of DNA motif sequences found in both cell types in common were listed.

FR and RF (96) FR and RF (96) FR and RF (96) FR and RF (96) FR (57) FR (57) RF (53) RF (53)

8 FR and RF (118) FR and RF (118) FR and RF (118) FR and RF (118)

Supplemental Table S6. Biased orientations of repeat DNA sequences in T cells. Score: –log10 (p-value).

Forward-reverse (FR) orientation Repeat DNA seq. Score MIRc 48.07

Using H3K27ac histone modification marks

Forward-reverse (FR) orientation Repeat DNA seq. Score L2 62.48 MIRc 28.32

Reverse-forward (RF) orientation Repeat DNA seq. Score AluSz 7.5

9 Supplemental Table S7. Co-location of biased orientations of DNA motif sequences in monocytes

Motif 1 Motif 2 # both # motif 1 # motif 2 # others p-value RAD21 RREB1 4836 1044 4300 15915 0 SOX TCF7L2 21268 0 129 124469 0 ETS2 SP1 4831 880 3542 16842 0 LEF1 TCF7L2 21268 0 126 124472 0 RAD21 SMAD2 4826 1054 4179 16036 0 LEF1 SOX 21268 129 126 124343 0 FOSB SMAD2 4820 795 4185 16295 0 DLX5 PRRX2 20580 0 128 125158 0 BRF1 RREB1 4815 4350 1153 15777 0 NFAT NFATC4 16105 0 110 129651 0 BRF1 SIRT6 4808 3472 1160 16655 0 ETV4 FLI1 15046 3276 0 127544 0 BRF1 SMARCC2 4800 3746 1168 16381 0 LEF1 SOX10 14773 24783 6621 99689 0 ETS2 RREB1 4789 922 4347 16037 0 SOX SOX10 14772 24784 6625 99685 0 ETS2 MAZ 4778 933 3183 17201 0 SOX10 TCF7L2 14744 6524 24812 99786 0 MLXIPL RREB1 4776 802 4360 16157 0 ELF5 ETV4 13205 5117 6384 121160 0 KLF3 ZNF219 4739 2266 1070 18020 0 ELF5 FLI1 12971 6618 2075 124202 0 ETS2 SMARCC2 4730 981 3816 16568 0 RUNX2 RUNX3 12875 3088 174 129729 0 SMAD2 XRCC4 4717 4288 1049 16041 0 RUNX1 RUNX3 12866 0 183 132817 0 PLAGL1 ZNF219 4678 3033 1131 17253 0 RUNX1 RUNX2 12866 3097 0 129903 0 HIC1 RREB1 4672 662 4464 16297 0 HMGA1 HMX1 12611 0 15149 118106 0 HIC1 SMAD2 4660 674 4345 16416 0 NFATC1 NFATC3 10877 231 0 134758 0 SMARCC2 XRCC4 4654 3892 1112 16437 0 NFATC1 NFATC4 10831 5274 277 129484 0 SMARCC2 ZNF219 4652 3894 1157 16392 0 NFAT NFATC1 10831 277 5384 129374 0 MLXIPL ZNF263 4628 950 4604 15913 0 NFAT NFATC3 10815 62 5400 129589 0 FOSB ZNF263 4613 1002 4619 15861 0 NFATC3 NFATC4 10815 5290 62 129699 0 ETS2 SIRT6 4609 1102 3671 16713 0 BHLHE40 MITF 10319 65 19796 115686 0 HIC1 SP1 4579 755 3794 16967 0 HOXA2 MEOX2 9999 0 125 135742 0 EGR2 KLF3 4557 1117 2448 17973 0 EMX1 MEOX2 9999 0 125 135742 0 MLXIPL SP1 4557 1021 3816 16701 0 BCL6 HMGA1 7648 4963 32936 100319 0 FOSB RREB1 4537 1078 4599 15881 0 MEIS1 MEIS3 6973 4122 13183 121588 0 CTCF SMAD2 4527 781 4478 16309 0 BHLHE40 TCF12 6343 23772 57 115694 0 SMAD2 ZNF143 4523 1130 4482 15960 0 HMGA1 STAT5A 4835 34254 2003 104774 0 MAZ SP2 4506 3455 946 17188 0 FOXD2 FOXL1 4606 0 6432 134828 0 MLXIPL PLAGL1 4505 1073 3206 17311 0 DLX3 DLX5 4561 24 16147 125134 0 SP2 ZNF263 4466 4766 986 15877 0 DLX5 MSX1 4561 24 16147 125134 0 KLF6 MLXIPL 4463 3032 1115 17485 0 ATF3 CREB 4549 0 7521 133796 0 HIC1 KLF6 4450 884 3045 17716 0 DLX3 PRRX2 4527 58 16053 125228 0 HIC1 ZNF263 4444 890 4788 15973 0 MSX1 PRRX2 4527 58 16053 125228 0 SMAD2 SP2 4443 4562 1009 16081 0 NFATC1 NFATC2 4324 0 6784 134758 0 EGR2 SP2 4385 2967 1067 17676 0 NFATC2 NFATC4 4324 0 11781 129761 0 CTCF RREB1 4379 929 4757 16030 0 NFAT NFATC2 4324 0 11891 129651 0 PARG SP1 4379 1016 3994 16706 0 NFATC2 NFATC3 4324 0 6553 134989 0 HIC1 PLAGL1 4359 975 3352 17409 0 EHF ELF5 4112 15477 64 126213 0 CTCF ZNF263 4357 951 4875 15912 0 EHF ETV4 4085 14237 91 127453 0 PARG SIRT6 4326 1069 3954 16746 0 EHF FLI1 4080 10966 96 130724 0 CTCF SP1 4321 987 4052 16735 0 DLX5 POU4F3 3960 16748 1943 123215 0 PARG SMARCC2 4321 1074 4225 16475 0 POU4F3 PRRX2 3943 16637 1960 123326 0 HIC1 MAZ 4285 1049 3676 17085 0 SOX30 SRY 3724 233 0 141909 0 RREB1 WT1 4252 4913 449 16481 0 TFAP2A TFAP2C 3705 6658 38 135465 0 SP1 WT1 4146 4227 555 17167 0 AP2A TFAP2A 3644 0 6719 135503 0 PITX1 SMAD2 4029 760 4976 16330 0 AP2A TFAP2C 3644 0 99 142123 0 ETS RREB1 4018 519 5118 16440 0 NR3C1 PGR 3246 3379 0 139241 0 E2F RREB1 3994 413 5142 16546 0 FOS JUN 3239 7653 1407 133567 0 EGR2 WT1 3985 3367 716 18027 0 MAZ ZIC1 2659 5901 1226 136080 0 ZBTB6 ZNF263 3972 694 5260 16169 0 MAFB MAFG 2608 13 36295 106950 0 SMAD2 ZBTB6 3968 5037 698 16392 0 EHF GTF2B 2558 30044 1618 111646 0 RREB1 YY1 3948 402 5217 16528 0 ZBTB7B ZIC1 2515 6045 0 137306 0 E2F SP1 3913 494 4460 17228 0 MAZ ZBTB7B 2503 1382 12 141969 0 HES1 SMAD2 3911 445 5094 16645 0 KLF2 SREBF2 2476 6129 1240 136021 0 MAZ WT1 3898 4063 803 17331 0 STAT5A TEAD3 2412 1606 36677 105171 0 E2F SMAD2 3896 511 5109 16579 0 ETV4 SPIC 2361 15961 32 127512 0 WT1 ZNF148 3894 2809 807 18585 0 FLI1 SPIC 2359 34 12687 130786 0 SMAD2 YY1 3885 465 5120 16625 0 KLF2 ZIC1 2310 6250 1406 135900 0 RREB1 ZBTB6 3883 5282 783 16147 0 EGR1 KLF6 2160 9 12931 130766 0 KLF6 WT1 3876 3619 825 17775 0 EMX1 MEOX1 2151 0 7973 135742 0 SMAD2 WT1 3876 5129 825 16265 0 HOXA2 MEOX1 2151 0 7973 135742 0 WT1 ZNF263 3869 5363 832 16031 0 DLX5 MEOX1 2124 27 18584 125131 0 SP1 YY1 3863 487 4510 17235 0 MEOX1 MEOX2 2123 7876 28 135839 0 PITX1 RREB1 3861 928 5275 16031 0 MEOX1 MSX1 2119 2466 32 141249 0 HES1 RREB1 3856 500 5309 16430 0 DLX3 MEOX1 2119 32 2466 141249 0 KLF6 ZNF143 3852 486 3643 18114 0 MEOX1 PRRX2 2107 44 18473 125242 0 SP1 ZNF143 3850 488 4523 17234 0 FOXI1 FOXL1 2073 2533 0 141260 0 ETS SP1 3845 692 4528 17030 0 FOXD2 FOXI1 2073 0 8965 134828 0 ETS SMAD2 3819 718 5186 16372 0 HMX1 SRY 1928 25832 1030 117076 0 E2F KLF6 3815 592 3680 18008 0 FOSL1 JUN 1906 1165 2740 140055 0 CTCF RAD21 3804 1504 225 20562 0 FOSL1 TCF7L2 1651 5 1420 142790 0 ATF3 SMAD2 3786 692 5219 16398 0 NR3C1 TCF7L2 1650 6 7 144203 0 KLF6 YY1 3777 573 3718 18027 0 FOSL1 NR3C1 1650 7 1421 142788 0 E2F ZNF263 3751 656 5481 16207 0 SOX6 ZNF384 1629 25620 608 118009 0 E2F EGR2 3746 661 3606 18082 0 EGR4 KLF10 1621 243 12947 131055 0 ZNF143 ZNF263 3738 600 5494 16263 0 AP-1 JUN 1595 432 3051 140788 0 SP1 ZBTB6 3735 4638 931 16791 0 FOXG1 FOXM1 1569 1014 3745 139538 0 HES1 SP1 3732 624 4641 17098 0 FOXM1 FOXO1 1569 1014 3745 139538 0 ETS ZNF263 3716 821 5516 16042 0 EGR1 KLF10 1555 614 13013 130684 0 HES1 KLF6 3705 651 3790 17949 0 HMX1 MNX1 1528 261 26232 117845 0 CTCF KLF6 3695 852 3800 17748 0 HOXA2 mix-a 1502 8622 7 135735 0 E2F MAZ 3694 713 4267 17421 0 EMX1 mix-a 1502 8622 7 135735 0 YY1 ZNF263 3694 656 5538 16207 0 EGR1 ETV4 1499 18 16823 127526 0 PTF1A SMAD2 3692 690 5313 16400 0 EGR1 FLI1 1498 19 13548 130801 0 EGR2 ZNF143 3684 654 3668 18089 0 DLX5 mix-a 1486 19222 23 125135 0 ETS KLF6 3665 872 3830 17728 0 MEOX2 mix-a 1482 8517 27 135840 0 HES1 ZNF263 3665 691 5567 16172 0 EMX1 LMX1A 1478 0 8646 135742 0 EGR2 YY1 3651 699 3701 18044 0 LMX1A MEOX2 1478 8521 0 135867 0 PLAGL1 YY1 3651 699 4060 17685 0 DLX5 LMX1A 1478 19230 0 125158 0 ETS MAZ 3636 901 4325 17233 0 HOXA2 LMX1A 1478 8646 0 135742 0 E2F PLAGL1 3635 772 4076 17612 0

10 ATF3 ZNF263 3627 851 5605 16012 0 FUBP1 KLF6 2567 344 4928 18256 0 ATF3 RREB1 3616 862 5520 16097 0 FUBP1 SP1 2543 368 5830 17354 0 MAZ YY1 3613 737 4348 17397 0 KLF16 RREB1 2536 6629 380 16550 0 PLAGL1 ZNF143 3612 726 4099 17658 0 PROX1 SMAD2 2534 318 6471 16772 0 HES1 PLAGL1 3601 755 4110 17629 0 RREB1 SP3 2530 6635 434 16496 0 MYOG SMAD2 3601 752 5404 16338 0 KLF16 SP3 2513 403 451 22728 0 MAZ ZNF143 3584 754 4377 17380 0 SIN3A SP1 2507 424 5866 17298 0 EGR2 HES1 3576 3776 780 17963 0 FUBP1 ZNF263 2493 418 6739 16445 0 PARG ZNF143 3558 780 4056 17701 0 PROX1 RREB1 2485 367 6651 16592 0 PTF1A ZNF263 3532 850 5700 16013 0 KLF6 SIN3A 2479 452 5016 18148 0 MYOG RREB1 3530 823 5606 16136 0 EGR2 FUBP1 2477 4875 434 18309 0 PARG YY1 3506 844 4108 17637 0 SIN3A ZNF263 2466 465 6766 16398 0 HES1 MAZ 3499 857 4462 17277 0 SP2 SP3 2464 500 2988 20143 0 HES1 PARG 3491 865 4123 17616 0 NFKB2 SMAD2 2453 510 6552 16580 0 SMAD2 TBP 3450 344 5555 16746 0 FUBP1 PLAGL1 2451 460 5260 17924 0 RREB1 TBP 3418 376 5718 16583 0 NFKB2 ZNF263 2442 521 6790 16342 0 SP1 TBP 3334 460 5039 17262 0 KLF16 SP1 2428 5945 488 17234 0 KLF5 RREB1 3315 5850 471 16459 0 PROX1 SP1 2428 424 5945 17298 0 KLF6 TBP 3308 486 4187 18114 0 FUBP1 PARG 2427 484 5187 17997 0 FOS RREB1 3300 238 5865 16692 0 SP1 SP3 2420 5953 544 17178 0 RREB1 RUNX2 3299 5837 358 16601 0 NFKB2 RREB1 2401 562 6735 16397 0 CEBPZ SMAD2 3297 497 5708 16593 0 PROX1 ZNF263 2399 453 6833 16410 0 KLF5 SP1 3287 5086 499 17223 0 FUBP1 MAZ 2391 520 5496 17688 0 RUNX2 SMAD2 3261 396 5744 16694 0 EGR2 SIN3A 2389 542 4963 18201 0 FOS SP1 3258 280 5115 17442 0 KLF6 PROX1 2388 5107 464 18136 0 PLAGL1 TBP 3225 569 4486 17815 0 PLAGL1 SIN3A 2376 555 5335 17829 0 GABPB1_GABPB2 ZNF263 3199 652 6048 16196 0 PSMD9 RREB1 2372 210 6793 16720 0 TBP ZNF263 3197 597 6035 16266 0 KLF16 SP2 2370 546 3082 20097 0 CEBPZ RREB1 3195 599 5941 16360 0 PSMD9 SP1 2365 217 6008 17505 0 GABPB1_GABPB2 SMAD2 3186 665 5819 16425 0 FUBP1 PITX3 2348 563 4552 18632 0 RUNX2 SP1 3176 481 5197 17241 0 PLAGL1 PROX1 2325 5386 527 17857 0 RREB1 SMAD4 3162 5974 310 16649 0 EGR2 PROX1 2293 5059 559 18184 0 SP1 SP4 3157 5216 342 17380 0 MAZ PROX1 2287 5674 565 17569 0 KLF6 RUNX2 3156 4339 501 18099 0 PARG PROX1 2287 565 5327 17916 0 EGR2 TBP 3145 649 4207 18094 0 MAZ PSMD9 2274 308 5687 17826 0 FOS SMAD2 3145 393 5860 16697 0 PSMD9 ZNF148 2270 312 4433 19080 0 EN1 SMAD2 3133 525 5872 16565 0 KLF6 PSMD9 2259 323 5236 18277 0 PARG TBP 3130 664 4484 17817 0 PSMD9 ZNF263 2251 331 6996 16517 0 RREB1 SP4 3121 6044 378 16552 0 EGR2 PSMD9 2250 332 5102 18411 0 GABPB1_GABPB2 RREB1 3118 733 6018 16226 0 PSMD9 SMAD2 2241 341 6764 16749 0 FOS KLF6 3118 420 4377 18180 0 NR2C2 ZNF263 2236 551 7011 16297 0 POU6F1 SMAD2 3114 482 5891 16608 0 RREB1 TRIM28 2196 6940 301 16658 0 EN1 SP1 3112 546 5261 17176 0 SMAD2 TRIM28 2172 6833 325 16765 0 EGR2 RUNX2 3099 4253 558 18185 0 KLF3 PSMD9 2155 427 4850 18663 0 RXRA SMAD2 3098 5907 681 16409 0 PSMD9 ZNF219 2151 431 3658 19855 0 CEBPZ ZNF263 3095 699 6137 16164 0 PSMD9 SMARCC2 2144 438 6402 17111 0 EGR2 FOS 3091 447 4261 18296 0 PLAGL1 PSMD9 2123 459 5588 17925 0 KLF5 ZNF148 3090 3613 696 18696 0 SP1 TRIM28 2070 6303 427 17295 0 SMAD4 SP1 3090 5283 382 17340 0 TRIM28 ZNF263 2050 7182 447 16416 0 FOS MAZ 3087 451 4874 17683 0 KLF14 RREB1 2049 7087 340 16619 0 RUNX2 ZNF263 3083 574 6149 16289 0 KLF6 TRIM28 2049 5446 448 18152 0 MAZ TBP 3081 713 4880 17421 0 HOXA7 RREB1 2043 252 7122 16678 0 NR3C1 ZNF263 3079 545 6168 16303 0 KLF14 SP1 2041 6332 348 17374 0 EN1 ZNF263 3079 579 6153 16284 0 PLAGL1 TRIM28 2019 5692 478 17906 0 RREB1 RXRA 3073 6063 706 16253 0 KLF3 TBP 1982 361 5023 18729 0 PITX3 TBP 3060 734 3840 18461 0 EBF1 RREB1 1979 7157 494 16465 0 KLF5 MAZ 3060 4901 726 17408 0 TBP ZNF219 1971 372 3838 19914 0 EN1 RREB1 3059 599 6077 16360 0 HOXA7 SP1 1963 332 6410 17390 0 CEBPZ SP1 3057 737 5316 16985 0 ATF3 SP1 1959 267 6414 17455 0 FOS ZNF263 3052 486 6180 16377 0 TBP ZNF148 1948 395 4755 18997 0 BDP1 RREB1 3050 730 6115 16200 0 RREB1 SP8 1932 7233 308 16622 0 PLAGL1 RUNX2 3037 4674 620 17764 0 HOXA7 SMAD2 1906 389 7099 16701 0 POU6F1 ZNF263 3035 561 6212 16287 0 HOXA7 MAZ 1899 396 6062 17738 0 MAZ RUNX2 3028 4933 629 17505 0 HOXA7 ZNF263 1898 397 7334 16466 0 NR3C1 SMAD2 3014 610 5991 16480 0 SP3 SP8 1890 1074 350 22781 0 SMAD2 SMAD4 2986 6019 486 16604 0 HOXA7 KLF6 1885 410 5610 18190 0 FOS PLAGL1 2967 571 4744 17813 0 EGR2 HOXA7 1864 431 5488 18312 0 EGR2 SP4 2952 4400 547 18196 0 ATF3 KLF6 1862 364 5633 18236 0 FOS KLF3 2948 590 4057 18500 0 KLF16 SP8 1862 1054 378 22801 0 EN1 KLF6 2944 714 4551 17886 0 SP2 SP8 1851 389 3601 20254 0 POLR3A RREB1 2942 6223 731 16199 0 SP1 SP8 1850 6523 390 17332 0 PARG RUNX2 2936 4678 721 17760 0 RREB1 ZIC1 1841 7295 210 16749 0 FOS ZNF148 2934 604 3769 18788 0 ATF3 EGR2 1840 386 5512 18357 0 FOS ZNF219 2933 605 2876 19681 0 SP1 ZIC1 1833 6540 218 17504 0 KLF6 SMAD4 2932 4563 540 18060 0 SMAD2 SMAD3 1823 7182 397 16693 0 EN1 PLAGL1 2931 727 4780 17657 0 GLI1 RREB1 1817 314 7319 16645 0 EGR2 SMAD4 2930 4422 542 18201 0 DNAAF2 RREB1 1816 7349 259 16671 0 EN1 MAZ 2928 730 5033 17404 0 SMAD2 TP53 1806 415 7199 16675 0 SMAD4 ZNF263 2915 6317 557 16306 0 ATF3 MAZ 1804 422 6083 17786 0 NR3C1 SIRT6 2913 711 5367 17104 0 RREB1 SMAD3 1792 7344 428 16531 0 MAZ SMAD4 2908 5053 564 17570 0 SMAD2 ZIC1 1789 7216 262 16828 0 MAZ SP4 2904 5057 595 17539 0 DNAAF2 SP1 1783 6590 292 17430 0 POU6F1 RREB1 2898 698 6238 16261 0 DNAAF2 SMAD2 1779 7226 296 16794 0 SP4 ZNF263 2892 6340 607 16256 0 EGR2 ZIC1 1748 5604 303 18440 0 SMAD2 SP4 2888 6117 611 16479 0 GLI1 SMAD2 1742 389 7263 16701 0 ETV5 SMAD2 2860 612 6145 16478 0 GLI1 SP1 1733 398 6640 17324 0 SP4 ZNF148 2855 3848 644 18748 0 KLF6 ZIC1 1728 5767 323 18277 0 KLF6 SP4 2850 4645 649 17951 0 ZIC1 ZNF263 1721 330 7511 16533 0 FOS SMARCC2 2839 699 5707 16850 0 GLI1 ZNF263 1709 422 7523 16441 0 ETV5 ZNF263 2835 637 6412 16211 0 KLF3 ZIC1 1698 5307 353 18737 0 SP2 SP4 2817 2635 682 19961 0 MAZ ZIC1 1697 6264 354 17780 0 PLAGL1 SMAD4 2799 4912 673 17711 0 PLAGL1 ZIC1 1695 6016 356 18028 0 PPARG ZNF263 2741 629 6491 16234 0 ISL1 SMAD2 1691 352 7314 16738 0 PPARG SMAD2 2711 659 6294 16431 0 DNAAF2 KLF6 1682 5813 393 18207 0 FUBP1 SMAD2 2671 240 6334 16850 0 ISL1 ZNF263 1679 364 7568 16484 0 FUBP1 RREB1 2633 278 6503 16681 0 DNAAF2 PLAGL1 1664 6047 411 17973 0 SIN3A SMAD2 2592 339 6413 16751 0 DNAAF2 EGR2 1662 5690 413 18330 0 RREB1 SIN3A 2589 342 6547 16617 0 ISL1 RREB1 1656 387 7480 16572 0

11 SP2 ZIC1 1642 409 3810 20234 0 SP1 ZBTB7B 591 118 7782 17604 1.12E-192 IKZF1 RREB1 1559 283 7606 16647 0 SMAD2 ZBTB7B 584 125 8421 16965 3.43E-162 TFAP2A TFAP2B 1534 96 150 24315 0 ZBTB7B ZNF263 571 138 8661 16725 5.99E-143 IKZF1 ZNF263 1522 320 7710 16543 0 PLAGL1 ZBTB7B 569 140 7142 18244 3.37E-197 KLF14 SP2 1518 283 3934 20360 0 GCM1 RREB1 265 62 8900 16868 3.66E-68 IKZF1 SP1 1509 333 6864 17389 0 ETS2 FLI1 251 7 24 25813 0 RFTN1 RREB1 1509 148 7627 16811 0 SP1 ZBTB7A 246 49 8127 17673 7.64E-80 TFAP2A TFAP2E 1499 131 69 24396 0 GATA6 SMAD2 232 8773 44 17046 2.18E-67 TFAP2B TFAP2E 1496 188 72 24339 0 GATA6 RREB1 225 8911 51 16908 3.52E-59 IKZF1 MAZ 1492 350 6395 17858 0 ETV3 FLI1 223 582 52 25238 0 KLF14 SP4 1490 311 2009 22285 0 GATA6 ZNF263 222 9025 54 16794 3.36E-55 KLF14 KLF16 1485 316 1431 22863 0 ETS2 ETV3 221 37 584 25253 0 RFTN1 SP1 1482 175 6891 17547 0 ETV2 FLI1 210 32 65 25788 0 RREB1 ZNF28 1473 7692 331 16599 0 ETS2 ETV2 201 41 57 25796 0 MYF6 RREB1 1471 7694 330 16600 0 STAT1 STAT5B 118 17 82 25878 0 NFE2 SMAD2 1471 210 7534 16880 0 STAT3 STAT5B 113 22 611 25349 0 MYF6 SMAD2 1463 7542 338 16752 0 ALX1 LBX2 22 2 2 26069 0 NFE2 RREB1 1460 221 7676 16738 0 RFTN1 SMAD2 1445 212 7560 16878 0 KLF14 SMAD2 1442 7563 359 16731 0 NKX2-5 ZNF263 1423 345 7824 16503 0 NFE2 SP1 1420 261 6953 17461 0 EGR2 RFTN1 1406 251 5946 18492 0 KLF6 RFTN1 1398 259 6097 18341 0 RFTN1 ZNF263 1385 272 7847 16591 0 KLF6 NFE2 1385 296 6110 18304 0 KLF3 RFTN1 1381 276 5624 18814 0 RREB1 TFAP2B 1375 309 7761 16650 0 NFE2 ZNF263 1374 307 7858 16556 0 SMAD2 TFAP2B 1374 310 7631 16780 0 MAZ RFTN1 1370 287 6517 17921 0 NFE2 PLAGL1 1369 312 6342 18072 0 PLAGL1 RFTN1 1367 290 6344 18094 0 RFTN1 ZNF148 1360 297 5343 19095 0 NFE2 PARG 1351 330 6263 18151 0 RFTN1 SP2 1335 322 4117 20321 0 RFTN1 ZNF219 1329 328 4480 19958 0 RREB1 TFAP2A 1326 304 7810 16655 0 DBP SMAD2 1322 288 7683 16802 0 SMAD2 TFAP2A 1320 310 7685 16780 0 DBP ZNF263 1296 314 7951 16534 0 RREB1 TFAP2E 1264 304 7872 16655 0 CTCF SMC3 1259 178 1977 22681 0 GTF2I ZNF263 1256 297 7991 16551 0 DNAAF2 ZNF263 1231 8001 216 16647 0 CTCF RXRA 1220 259 2559 22057 0 RAD21 RXRA 1206 239 2573 22077 0 RAD21 SMC3 1193 244 2836 21822 0 DNAAF2 PARG 1186 6428 261 18220 0 DNAAF2 PITX3 1166 5734 281 18914 0 RREB1 ZIC2 1160 185 7976 16774 0 RREB1 ZNF676 1136 8000 161 16798 0 SMAD2 ZIC2 1131 214 7874 16876 0 SP1 ZNF676 1119 7254 178 17544 0 SP1 ZIC2 1111 234 7262 17488 0 KLF6 ZIC2 1098 247 6397 18353 0 ZIC2 ZNF263 1096 249 8151 16599 2.35E-287 SMAD2 ZNF676 1069 7936 228 16862 6.00E-303 ZNF263 ZNF676 1062 8170 235 16628 2.99E-282 KLF6 ZNF676 1047 6448 250 18350 0 SMAD2 ZNF716 1046 7959 261 16829 7.20E-276 SMAD2 SULT1A2 967 107 8038 16983 0 RREB1 ZNF521 955 8181 236 16723 6.03E-245 RXRA SMC3 944 2835 218 22098 0 RREB1 ZNF770 932 8233 133 16797 2.76E-292 RREB1 SULT1A2 921 153 8215 16806 4.00E-277 SULT1A2 ZNF263 911 163 8321 16700 5.70E-262 KLF6 SULT1A2 895 179 6600 18421 0 RREB1 ZIC3 892 8244 142 16817 8.15E-272 SP1 SULT1A2 890 184 7483 17538 1.09E-289 PAX5 SMAD2 888 8117 219 16871 6.06E-234 PLAGL1 SULT1A2 881 193 6830 18191 1.48E-323 PARG SULT1A2 874 200 6740 18281 1.48E-322 SMAD2 ZIC3 865 8140 169 16921 9.77E-252 PITX3 SULT1A2 864 210 6036 18985 0 ZIC3 ZNF263 848 186 8384 16677 2.96E-224 PLAGL1 ZIC3 844 6867 190 18194 2.21E-306 SP1 ZIC3 842 7531 192 17530 4.32E-263 KLF6 ZIC3 830 6665 204 18396 2.75E-305 RREB1 ZNF202 804 8361 182 16748 2.79E-212 CREM SMAD2 753 170 8252 16920 1.46E-205 PAX8 RREB1 737 144 8428 16786 1.68E-206 PAX8 SMAD2 713 168 8292 16922 1.26E-190 HOMEZ RREB1 659 95 8506 16835 5.06E-204 BBX RREB1 653 132 8512 16798 5.57E-180 RREB1 ZNF316 641 8495 113 16846 4.55E-187 SMAD2 ZNF112 639 8366 135 16955 9.46E-179 HOMEZ SMAD2 636 118 8369 16972 4.03E-187 E2F3 SMAD2 634 8371 119 16971 9.93E-186 HOMEZ ZNF263 630 124 8602 16739 5.81E-173 E2F3 RREB1 627 8509 126 16833 4.04E-174 RREB1 ZBTB7B 623 86 8513 16873 3.98E-196 SMAD2 ZNF316 620 8385 134 16956 1.12E-171 HOMEZ SP1 615 139 7758 17583 3.35E-191 SMAD2 612 8393 109 16981 1.44E-182 HOMEZ MAZ 612 142 7275 18066 2.99E-209 SP1 ZNF316 608 7765 146 17576 3.68E-184 E2F2 RREB1 603 8562 118 16812 4.34E-168

12 Supplemental Table S8. Top 30 of co-locations of biased orientations of DNA binding motif sequences of transcription factors in T cells. Co-locations of DNA motif sequence of CTCF with another biased orientation of DNA motif sequence were shown in a separate table.

Co-locations of twelve pairs of DNA motif sequences were found in both monocytes and T cells, which were shown in a right table. All co-locations of biased orientations of DNA motif sequences in T cells were shown in the next page. Motif 1,2: DNA binding motif sequences of transcription factors. # both: the number of open chromatin regions including both Motif 1 and

Motif 2. # motif 1: the number of open chromatin regions including Motif 1. # motif 2: the number of open chromatin regions including Motif 2. # others: the number of open chromatin regions not including Motif 1 and Motif 2. Total number of open chromatin regions is 102,152.

Motif 1 Motif 2 # both # motif 1 # motif 2 # others p-value Motif 1 Motif 2 CTCF RAD21 2081 673 8 99390 0 EGR2 ZIC1 CTCF ZXDC 1105 634 30813 69600 3.09E-171 AP-1 JUN CTCF ZBTB7A 475 11 7574 94092 0 RUNX1 RUNX2 CTCF LRF 471 458 15 101208 0 FOSL1 JUN CTCF CTCFL 142 1597 63 100350 3.62E-201 AP2A TFAP2C CTCF REST 136 20911 87 81018 2.90E-39 KLF2 SREBF2 CTCFL RAD21 962 4350 9 96831 0 FOS JUN CTCFL ZBTB7A 929 0 7120 94103 0 KLF2 ZIC1 CTCFL REST 124 20923 82 81023 3.99E-35 CTCF RAD21 ELF5 ETV4 Motif 1 Motif 2 # both # motif 1 # motif 2 # others p-value EGR2 SP1 ETV4 ETV6 13650 142 0 88360 0 KLF10 KLF4 ELF3 ETV4 13641 0 151 88360 0 KLF10 SP1 ELF3 ETV6 13568 73 82 88429 0 CTCFL RAD21 EGR2 ZXDC 13177 7175 18741 63059 0 REST ZXDC 12849 8198 19069 62036 0 MZF1 ZXDC 10095 2760 21823 67474 0 EPAS1 HIF1A 10045 80 63 91964 0 BCL REST 9682 11365 3763 77342 0 ETS1 SPI1 9596 2651 22351 67554 0 KLF10 ZXDC 9564 22354 3558 66676 0 ETV4 SPI1 9059 2153 22888 68052 0 E2F3 REST 8800 12247 4072 77033 0 POU3F2 SOX5 8522 3601 10137 79892 0 BCL ZXDC 8222 5223 23696 65011 0 HOXB3 VAX1 8139 101 0 93912 0 E2F3 KLF10 8048 4824 5074 84206 0 KLF10 REST 7941 13106 5181 75924 0 KLF KLF5 7913 2115 2495 89629 0 KLF ZXDC 7891 24027 2517 67717 0 E2F3 ZXDC 7848 5024 24070 65210 0 KLF5 ZXDC 7777 24141 2251 67983 0 ETS1 ETV4 7777 3435 4470 86470 0 CACD ZXDC 7715 3845 24203 66389 0 CACD KLF 7591 3969 2817 87775 0 IKZF1 KLF4 7561 21658 4869 68064 0 PAX4 ZXDC 7390 138 24528 70096 0 CACD EGR2 7281 4279 13071 77521 0 EGR2 KLF 7225 13127 3183 78617 0 CACD KLF5 7147 4413 2881 87711 0 CACD KLF10 7066 4494 6056 84536 0

13 Motif 1 Motif 2 # both # motif 1 # motif 2 # others p-value AP2A TFAP2C 2849 0 84 99219 0 ETV4 ETV6 13650 142 0 88360 0 SOX17 SOX30 2832 7418 157 91745 0 ELF3 ETV4 13641 0 151 88360 0 KLF5 KLF7 2817 810 7211 91314 0 ELF3 ETV6 13568 73 82 88429 0 KLF2 PAX4 2801 4727 575 94049 0 EGR2 ZXDC 13177 7175 18741 63059 0 NFIA+NFIB+NFIC+NFIXNFIB 2780 1801 4520 93051 0 REST ZXDC 12849 8198 19069 62036 0 KLF7 REST 2770 18277 857 80248 0 MZF1 ZXDC 10095 2760 21823 67474 0 EP300 ETV4 2766 8446 1200 89740 0 EPAS1 HIF1A 10045 80 63 91964 0 HOXA11 HOXD11 2726 0 1946 97480 0 BCL REST 9682 11365 3763 77342 0 ZIC3 ZXDC 2700 670 29218 69564 0 ETS1 SPI1 9596 2651 22351 67554 0 E2F3 SP1 2618 10254 42 89238 0 KLF10 ZXDC 9564 22354 3558 66676 0 RAD21 ZXDC 2580 1505 29338 68729 0 ETV4 SPI1 9059 2153 22888 68052 0 EP300 SPI1 2579 29368 1387 68818 0 E2F3 REST 8800 12247 4072 77033 0 EGR2 KLF2 2550 17802 826 80974 0 POU3F2 SOX5 8522 3601 10137 79892 0 CACD KLF2 2543 9017 833 89759 0 BCL ZXDC 8222 5223 23696 65011 0 FOXB1 FOXD3 2516 33 977 98626 0 HOXB3 VAX1 8139 101 0 93912 0 KLF2 SREBF2 2373 5750 1003 93026 0 E2F3 KLF10 8048 4824 5074 84206 0 FOXK1 FOXO1A 2372 1451 4732 93597 0 KLF10 REST 7941 13106 5181 75924 0 AP-1 FOS 2313 2415 0 97424 0 KLF KLF5 7913 2115 2495 89629 0 FOS FOSB 2297 16 2393 97446 0 KLF ZXDC 7891 24027 2517 67717 0 FOS JUN 2268 6456 45 93383 0 E2F3 ZXDC 7848 5024 24070 65210 0 FOXD3 FOXP3 2252 12195 1241 86464 0 KLF5 ZXDC 7777 24141 2251 67983 0 BCL KLF7 2251 11194 1376 87331 0 ETS1 ETV4 7777 3435 4470 86470 0 FOXO1A FOXO3 2237 1239 4867 93809 0 CACD ZXDC 7715 3845 24203 66389 0 KLF KLF2 2225 8183 1151 90593 0 CACD KLF 7591 3969 2817 87775 0 KLF4 ZIC3 2190 1180 27029 71753 0 IKZF1 KLF4 7561 21658 4869 68064 0 ZIC1 ZIC3 2156 5502 1214 93280 0 PAX4 ZXDC 7390 138 24528 70096 0 KLF2 ZIC1 2131 5527 1245 93249 0 CACD EGR2 7281 4279 13071 77521 0 REST SP1 2124 18923 536 80569 0 EGR2 KLF 7225 13127 3183 78617 0 KLF2 KLF5 2122 7906 1254 90870 0 CACD KLF5 7147 4413 2881 87711 0 POU3F2 SOX30 2118 871 16541 82622 0 CACD KLF10 7066 4494 6056 84536 0 CTCF RAD21 2081 673 8 99390 0 KLF KLF4 6924 22295 3484 69449 0 ELF5 SPI1 2027 392 29920 69813 0 EGR2 KLF5 6753 13599 3275 78525 0 KLF7 SP1 1849 1778 811 97714 0 EN1 SPI1 6542 3417 25405 66788 0 ETF SP1 1808 13 852 99479 0 POU3F2 SRY 6531 39 12128 83454 0 ETF KLF5 1806 15 8222 92109 0 ZIC1 ZXDC 6456 1202 25462 69032 0 FOS FOSL1 1804 509 1166 98673 0 KLF KLF10 6409 3999 6713 85031 0 CACD ETF 1803 9757 18 90574 0 KLF REST 6311 14736 4097 77008 0 ETF KLF 1801 20 8607 91724 0 KLF4 KLF5 6214 23005 3814 69119 0 FOS FOSL2 1799 514 1171 98668 0 GATA2 GATA5 5947 0 3797 92408 0 FOS JUND:FRA1 1796 517 1159 98680 0 SREBF2 ZXDC 5788 2335 26130 67899 0 E2F3 ETF 1788 11084 33 89247 0 KLF4 ZIC1 5766 1892 23453 71041 0 ETF KLF10 1787 34 11335 88996 0 KLF4 MAZ 5635 20 23584 72913 0 FOS SMARCC1 1783 1148 530 98691 0 FOXD3 POU3F2 5549 20 13110 83473 0 TFAP2C ZXDC 1760 30158 1173 69061 2.71E-232 FOXD3 SOX5 5508 6615 61 89968 0 ELF5 ETS1 1741 678 10506 89227 0 FOXM1 FOXP3 5296 9151 24 87681 0 ELF5 ETV4 1724 9488 695 90245 0 LEF1 TCF4 5169 26 33 96924 0 CACD KLF4 1695 9865 18 90574 0 EGR2 ZIC1 5163 2495 15189 79305 0 ETV5 SPI1 1665 30282 1010 69195 3.41E-244 SOX5 SRY 5033 1537 7090 88492 0 BCL SP1 1633 11812 1027 87680 0 KLF ZIC1 5015 2643 5393 89101 0 FOXB1 FOXP3 1630 12817 919 86786 0 DLX3 MXI1 4922 0 57 97173 0 DLX3 PDX1 1552 4054 903 95643 0 AP-1 FOSB 4690 38 0 97424 0 DLX3 MSX3 1494 1466 961 98231 0 MAZ ZXDC 4688 967 27230 69267 0 ETF REST 1438 19609 383 80722 0 FOXO1 FOXO4 4657 42 35 97418 0 EGR2 SP1 1434 140 18918 81660 0 EGR2 PAX4 4654 2874 15698 78926 0 CLOCK:ARNTLEPAS1 1428 0 8680 92044 0 AP-1 JUN 4639 89 4085 93339 0 CLOCK:ARNTLHIF1A 1428 0 8697 92027 0 FOSB JUN 4636 4088 54 93374 0 NFKB1 SPI1 1426 30521 855 69350 2.68E-211 FOXO1 SOX5 4615 77 7508 89952 0 JUNB SMARCC1 1399 1532 0 99221 0 FOXO4 SOX5 4615 84 7508 89945 0 FOSL2 JUNB 1399 0 1571 99182 0 KLF4 SALL4 4245 24974 962 71971 0 JUNB JUND:FRA1 1399 0 1556 99197 0 SPI1 SPIB 4131 0 27816 70205 0 FOSL1 JUNB 1399 0 1571 99182 0 SALL4 ZXDC 3926 27992 1281 68953 0 NR2C2 ZXDC 1317 256 30601 69978 0 SOX10 SOX4 3804 10255 20 88073 0 SOX10 SOX18 1311 12748 36 88057 0 FOXD3 FOXO1 3729 3929 1840 92654 0 ETF KLF7 1276 2351 545 97980 0 FOXD3 SRY 3673 2897 1896 93686 0 SP1 ZXDC 1273 301 30645 69933 0 REST TCF12 3666 17381 1869 79236 0 E2F3 NR2C2 1272 301 11600 88979 0 EGR2 SALL4 3593 16759 1614 80186 0 KLF10 NR2C2 1257 316 11865 88714 0 CACD KLF7 3526 8034 101 90491 0 CACD SP1 1244 10316 330 90262 0 FOXO4 POU3F2 3424 1275 15235 82218 0 ETF ZXDC 1204 30714 617 69617 1.44E-208 FOXO1 POU3F2 3418 1274 15241 82219 0 KLF4 KLF7 1150 2477 563 97962 0 RUNX1 RUNX2 3168 9918 38 89028 0 BPTF FOXO1A 1145 382 5959 94666 0 E2F3 KLF7 3136 9736 491 88789 0 EGR2 ETF 1133 19219 688 81112 0 KLF2 ZXDC 3106 28812 270 69964 0 E2F3 KLF4 1132 11740 581 88699 0 KLF10 KLF7 3106 521 10016 88509 0 LTF SPI1 1130 445 30817 69760 4.56E-242 ZEB ZEB1 3053 1584 3693 93822 0 KLF3 KLF7 1125 2502 9 98516 0 KLF KLF7 3051 576 7357 91168 0 NR2C2 REST 1115 19932 458 80647 0 FOXO1 SRY 3030 3540 1662 93920 0 CTCF ZXDC 1105 634 30813 69600 3.09E-171 FOXO4 SRY 3029 3541 1670 93912 0 KLF10 KLF3 1100 12022 34 88996 0 AP-1 FOSL1 2970 1758 0 97424 0 KLF10 KLF4 1099 12023 614 88416 0 MSX3 PDX1 2960 2646 0 96546 0 CACD KLF3 1098 10462 36 90556 0 AP-1 FOSL2 2959 1769 11 97413 0 KLF KLF3 1097 9311 37 91707 0 FOSL1 FOSL2 2958 12 12 99170 0 E2F3 KLF3 1094 11778 40 89240 0 PURA SMAD5 2956 10331 1194 87671 0 KLF4 REST 1059 19988 654 80451 2.20E-306 AP-1 JUND:FRA1 2955 1773 0 97424 0 HOXB4 VAX1 1048 7091 0 94013 0 FOSL1 JUND:FRA1 2955 0 15 99182 0 HOXB3 HOXB4 1048 7192 0 93912 0 FOSB FOSL2 2945 25 1745 97437 0 KLF5 SP1 1018 556 9010 91568 0 FOSB FOSL1 2945 25 1745 97437 0 KLF SP1 1013 561 9395 91183 0 FOSB JUND:FRA1 2944 11 1746 97451 0 KLF10 SP1 1008 566 12114 88464 0 FOSL2 JUND:FRA1 2943 12 27 99170 0 IKZF1 IRF1 976 536 11454 89186 0 AP-1 SMARCC1 2931 0 1797 97424 0 KLF3 REST 975 20072 159 80946 0 FOSB SMARCC1 2931 0 1759 97462 0 ETS1 LTF 967 11280 608 89297 0 FOSL2 SMARCC1 2931 0 39 99182 0 CTCFL RAD21 962 4350 9 96831 0 FOSL1 SMARCC1 2931 0 39 99182 0 CTCFL ZBTB7A 929 0 7120 94103 0 JUND:FRA1 SMARCC1 2931 0 24 99197 0 LRF ZBTB7A 929 0 7120 94103 0 FOSL2 JUN 2918 5806 52 93376 0 KLF KLF8 913 5 9495 91739 0 FOSL1 JUN 2918 5806 52 93376 0 CACD KLF8 912 10648 6 90586 0 JUN JUND:FRA1 2914 5810 41 93387 0 EGR2 KLF8 910 19442 8 81792 0 JUN SMARCC1 2913 18 5811 93410 0 KLF10 KLF8 909 9 12213 89021 0

14 E2F3 KLF8 908 11964 10 89270 0 JDP2 JUND:FRA1 460 0 2495 99197 0 KLF3 KLF5 902 9126 232 91892 0 FOSB JUND:FOSL2 460 1 4230 97461 0 FOS JUN:FOSB 811 1502 0 99839 0 FOS MAF 460 5 4247 97440 0 JUN:FOSB JUND:FRA1 811 2144 0 99197 0 FOSB JUND:FOS 460 4 4230 97458 0 FOSL1 JUN:FOSB 811 0 2159 99182 0 JUND:FOS SMARCC1 458 2473 6 99215 0 AP-1 JUN:FOSB 811 3917 0 97424 0 JUNB:FOS SMARCC1 458 2473 5 99216 0 FOSL2 JUN:FOSB 810 1 2160 99181 0 JUN:FOSL1 SMARCC1 458 2473 6 99215 0 FOSB JUN:FOSB 810 1 3880 97461 0 JUNB JUND 458 941 3 100750 0 JUN:FOSB SMARCC1 808 2123 3 99218 0 JDP2 JUNB 458 2 941 100751 0 BCL KLF3 808 12637 326 88381 0 JUNB JUND:FOS 458 941 6 100747 0 JUN:FOSB JUNB 807 592 4 100749 0 JUN:FOSL1 JUNB 458 941 6 100747 0 JUN JUN:FOSB 797 7927 14 93414 0 JUNB JUND:FOSL2 458 941 3 100750 0 FOXA1 FOXB1 793 1756 9 99594 0 JDP2 SMARCC1 458 2473 2 99219 0 FOXA1 FOXD3 782 2711 20 98639 0 JUNB JUNB:FOS 458 5 941 100748 0 KLF3 SP1 735 1925 399 99093 0 JUND SMARCC1 458 2473 3 99218 0 KLF8 REST 729 20318 189 80916 2.173889e-322 JUND:FOSL2SMARCC1 458 2473 3 99218 0 KLF5 KLF8 722 196 9306 91928 0 JUN MAF 457 8 8267 93420 0 ELF1 ELF3 715 8 12926 88503 0 JUN JUN:FOSL1 451 8273 13 93415 0 ELF1 ETV6 715 8 12935 88494 0 JUN JUND 451 8273 10 93418 0 KLF8 ZXDC 709 209 31209 70025 2.81E-182 JUN JUND:FOSL2 451 8273 10 93418 0 NKX2-1 NKX3-2 667 11235 18 90232 0 JUN JUND:FOS 451 8273 13 93415 0 ELF1 ETS1 626 181 8023 93322 0 JUN JUNB:FOS 451 8273 12 93416 0 BCL KLF8 588 12857 330 88377 4.61E-284 JDP2 JUN 451 8273 9 93419 0 HOXA11 HOXB13 523 4149 231 97249 0 TCF4 ZEB 384 210 6362 95196 3.36E-298 SP2 TCF12 517 5018 2 96615 0 ZNF263 ZXDC 369 97 31549 70137 3.39E-101 SP2 ZBTB7A 517 1243 2 100390 0 NFIB NFKB1 343 2 6957 94850 0 ELF1 SPI1 512 295 31435 69910 3.58E-79 ETF SP2 343 6 1478 100325 0 HOXB13 HOXD11 512 2214 242 99184 0 GSX1 PDX1 343 5263 4 96542 0 BPTF SOX5 506 297 11617 89732 1.34E-260 CACD SP2 340 11220 9 90583 1.40E-307 BPTF FOXO1 502 301 11538 89811 1.50E-257 NFIC NFKB1 340 7581 5 94226 0 FOXA1 FOXP3 502 13945 300 87405 6.13E-221 NFIA+NFIB+NFIC+NFIXNFKB1 339 4242 6 97565 0 EPAS1 MAZ 491 260 9617 91784 4.72E-301 KLF5 SP2 339 10 9689 92114 0 HIF1A MAZ 487 264 9638 91763 1.04E-295 SP1 SP2 338 11 2322 99481 0 AP-1 JUNB 485 0 4243 97424 0 KLF SP2 337 12 10071 91732 6.289625e-316 BPTF SRY 484 319 10045 91304 2.13E-264 KLF10 SP2 337 12 12785 89018 1.13E-281 FOS JUNB 482 3 4225 97442 0 E2F3 SP2 335 12537 14 89266 5.20E-280 FOSB JUNB 482 3 4208 97459 0 REST SP2 334 20713 15 81090 2.27E-206 JUN JUNB 475 10 8249 93418 0 JUNB MAF 302 163 2668 99019 0 CTCF ZBTB7A 475 11 7574 94092 0 FOSL2 MAF 302 163 2668 99019 0 CTCF LRF 471 458 15 101208 0 FOSL1 MAF 300 165 2670 99017 0 KLF4 ZNF263 466 0 28753 72933 3.41E-255 JUND:FRA1 MAF 298 167 2657 99030 0 JUN:FOSL1 JUNB:FOS 463 0 1 101688 0 MAF SMARCC1 296 2635 169 99052 0 CREB1 E4F1 463 199 296 101194 0 KLF1 KLF5 282 2 9746 92122 4.88E-282 AP-1 MAF 463 4265 2 97422 0 CACD KLF1 278 11282 6 90586 1.49E-253 JUNB:FOS JUND:FOS 463 0 1 101688 0 EGR2 SP2 270 20082 79 81721 2.97E-118 FOS JUN:FOSL1 462 1851 2 99837 0 FOXL1 POU3F2 266 41 18393 83452 4.22E-150 FOS JUND:FOS 462 1851 2 99837 0 KLF7 SP2 264 3363 85 98440 5.88E-306 AP-1 JUNB:FOS 462 4266 1 97423 0 FOXL1 SOX5 260 47 11863 89982 4.13E-189 AP-1 JUND:FOS 462 4266 2 97422 0 FOXL1 SRY 254 6316 53 95529 8.85E-247 FOSL2 JUN:FOSL1 462 2 2508 99180 0 EPAS1 MYC 247 0 9861 92044 4.80E-250 AP-1 JUN:FOSL1 462 4266 2 97422 0 HIF1A MYC 247 0 9878 92027 7.31E-250 FOSL1 JUNB:FOS 462 1 2508 99181 0 CLOCK:ARNTLMYC 246 1182 1 100723 0 FOSL2 JUND:FOS 462 2 2508 99180 0 EGR2 KLF1 238 46 20114 81754 6.74E-119 FOSL1 JUN:FOSL1 462 2 2508 99180 0 SP2 ZXDC 229 120 31689 70114 1.53E-39 FOSL1 JUND:FOS 462 2 2508 99180 0 KLF1 ZXDC 228 56 31690 70178 3.70E-65 FOS JUNB:FOS 462 1851 1 99838 0 KLF KLF1 222 62 10186 91682 3.43E-161 JUND JUND:FOS 461 3 0 101688 0 BCL SP2 214 13231 135 88572 3.63E-98 JUND:FOSL2JUND:FRA1 461 2494 0 99197 0 FOXD3 FOXL1 214 93 5355 96490 1.63E-194 FOSL2 JUNB:FOS 461 2 2509 99180 0 FOXA2 POU3F2 213 5 18446 83488 2.88E-149 FOS JUND:FOSL2 461 1852 0 99839 0 FOXA2 SRY 212 6358 6 95576 8.72E-244 JUN:FOSB JUND:FOSL2 461 0 350 101341 0 MYC MYOD1 211 36 4400 97505 6.31E-244 JUN:FOSB JUND:FOS 461 3 350 101338 0 TBX2 TBX5 201 0 872 101079 0 JUNB:FOS JUND:FOSL2 461 2 0 101689 0 FOXL1 FOXO1 200 107 4492 97353 2.72E-187 FOSL1 JUND 461 0 2509 99182 0 FOXL1 FOXO4 199 108 4500 97345 1.47E-185 JUND:FOS JUND:FOSL2 461 0 3 101688 0 FOXJ2:ELF1 SPI1 194 31753 0 70205 7.77E-99 FOSL2 JUND 461 0 2509 99182 0 ELF5 FOXJ2:ELF1 194 1745 0 100213 0 JUNB:FOS JUND:FRA1 461 2 2494 99195 0 FOXJ2:ELF1 SPIB 193 3938 1 98020 3.05E-269 JUN:FOSL1 JUND:FRA1 461 2494 3 99194 0 ETV4 FOXJ2:ELF1 193 11019 1 90939 2.51E-184 JUNB:FOS JUND 461 2 0 101689 0 ELF1 ELF5 185 1754 3 100210 4.358871e-317 JUN:FOSL1 JUND 461 0 3 101688 0 EP300 KLF4 184 85 29035 72848 1.28E-41 AP-1 JUND 461 4267 0 97424 0 CLOCK:ARNTLUSF 181 1247 0 100724 0 JUN:FOSL1 JUND:FOSL2 461 0 3 101688 0 HIF1A USF 181 0 9944 92027 4.67E-183 AP-1 JUND:FOSL2 461 4267 0 97424 0 EPAS1 USF 181 0 9927 92044 3.43E-183 JUN:FOSB JUN:FOSL1 461 350 3 101338 0 ELF3 FOXJ2:ELF1 179 13462 15 88496 1.21E-136 FOSL1 JUND:FOSL2 461 0 2509 99182 0 ETV6 FOXJ2:ELF1 178 16 13472 88486 1.00E-134 FOS JUND 461 1852 0 99839 0 NFIL3 TEF 163 0 235 101754 0 JUND:FOS JUND:FRA1 461 2494 3 99194 0 MYOD1 USF 159 22 4452 97519 3.52E-188 JUN:FOSB JUNB:FOS 461 2 350 101339 0 NKX2-2 TCF3 156 0 2349 99647 4.81E-254 JUND JUND:FOSL2 460 1 1 101690 0 NR2F1 RARB 154 6356 95 95547 1.25E-117 JUND JUND:FRA1 460 2495 1 99196 0 RARB VDR:RXRA 154 95 6356 95547 1.25E-117 FOSL1 JDP2 460 0 2510 99182 0 CTCF CTCFL 142 1597 63 100350 3.62E-201 FOSB MAF 460 5 4230 97457 0 CTCF REST 136 20911 87 81018 2.90E-39 AP-1 JDP2 460 4268 0 97424 0 HEY2 REST 136 20911 67 81038 4.12E-46 JDP2 JUNB:FOS 460 0 3 101689 0 ETS1 FOXJ2:ELF1 136 12111 58 89847 2.86E-79 FOSB JUN:FOSL1 460 4 4230 97458 0 NEUROD2 NKX2-2 131 25 738 101258 1.06E-247 FOSB JDP2 460 0 4230 97462 0 TAF1 YY1 130 783 67 101172 8.09E-218 FOSL2 JDP2 460 0 2510 99182 0 E2F6 EGR2 128 20224 55 81745 2.20E-48 JDP2 JUND:FOS 460 0 4 101688 0 CTCFL REST 124 20923 82 81023 3.99E-35 JUN:FOSB JUND 460 1 351 101340 0 E2F6 KLF4 123 29096 60 72873 4.58E-27 FOSB JUND 460 1 4230 97461 0 MYC USF 122 125 59 101846 2.20E-287 ELF1 ETV4 460 10752 263 90677 3.03E-254 E2F6 SPI1 114 31833 69 70136 6.51E-18 FOS JDP2 460 0 1853 99839 0 E2F6 IKZF1 110 12320 73 89649 2.41E-53 JDP2 JUN:FOSL1 460 0 4 101688 0 CEBPA NFIL3 102 61 3181 98808 6.80E-109 FOSL2 JUND:FOSL2 460 1 2510 99181 0 NFE2L1 REST 92 20955 39 81066 3.12E-34 FOSB JUNB:FOS 460 3 4230 97459 0 NKX2-2 NKX3-2 90 54 11812 90196 1.60E-47 JDP2 JUN:FOSB 460 0 351 101341 0 EHF SPI1 81 1 31866 70204 6.81E-40 JDP2 JUND 460 0 1 101691 0 EGR1 EGR2 53 1 20299 81799 3.02E-36 JDP2 JUND:FOSL2 460 0 1 101691 0 EGR1 REST 51 20996 3 81102 1.23E-31

15 EHF ETV4 51 11161 31 90909 1.16E-28 E2F3 EGR1 51 3 12821 89277 2.02E-42 CACD EGR1 49 5 11511 90587 6.89E-41 EGR1 KLF5 47 7 9981 92117 3.33E-40 EGR1 KLF 47 7 10361 91737 1.87E-39 EGR1 KLF10 45 9 13077 89021 1.17E-31 EGR1 ZXDC 40 14 31878 70220 1.24E-10 EGR1 SP1 37 17 2623 99475 5.74E-46 EGR1 ETF 34 20 1787 100311 5.78E-46

16