KCTD13 PROX1

IRF3

KLRG1

TJP1

COL12A1

LMBRD2

SLC25A32

TRO

RASD1

HECW2 CXCR4 IRF2BPL

PTPDC1

CD55 PSAT1 A MOV10L1SPRED2 TSGA10

BAIAP2 SLC1A4 TMEM39A

PPAP2B

BCL3 ARL4A

RAPGEF1

VEGFC F3 PHLDB2 UNC5B PRDM1

LEPREL1 NR4A2 NR4A1 RAPH1

SOCS6 SULT1B1 TNFAIP3

RGS2

GIMAP1 KIAA0513 STEAP2 HSP90B1 MAP3K8 SLC25A25 TNFRSF1B DDIT4 PLEKHA1 FRMD6 C2CD4A

TSPAN11

IGIP

UACA RFX2 PMAIP1

IL15RA

SLC2A12 MOSPD1 GIMAP6 EDN1 ADAM19 NCOA7

CLDN5 CHSY3 BCAP29

PDP1 UBE2J1 RBPMS2 PPFIBP2 KAT2B PLAU SIPA1L3 FOXN3 C14orf93 KIF26A EGR1 ACER2 MEI1 GAB1 ASUN

CNN3 SIRT1

RALGPS2 PPM1H TOX2 FAM174A DNAJB4 KLF11

GBE1 CHN2 TRIM2 IL1R1 KCNJ2 TFPI2 KLF2 PPP1R3B PPARA PPP1R15B VEGFA DSE CCRN4L NR2F2 AXL EXOC8 CCNA1 B4GALT1 GIMAP7 RQCD1 ITPRIP MYADM ICAM3

FGF2 HEY1 NFIL3

CTH PTP4A3 ATP2B1 EXT1 KLHL3 KLF9 COL13A1

MID2 GDPD1

EHD3 STRBP P4HA1 OSBP2

SEC11C NFAT5 PDGFD

ENC1 DUSP5 NRCAM ANO6 KLF10 SLC40A1 C2CD4B MEIS1HOXB2_ELF1 GIMAP2 SEMA6A NR4A3 KDM6B

MYO1D FAM193A

CSRNP2 RASGRF2 APOO ESYT2 NINL FOXP1 HDAC9 CLK1 CDK6 SCAMP5 PHLDB3 ASGR1

HELLS DIEXF SULT1C4 MBNL1 TRAF5 GIMAP8 FOXJ2_ELF1 SIX4 TEAD4_ERG ARL4C

EGR3 BACH1 ITGA6 LRRC8B MFSD2A SLC4A7

RDX

PLAT PODXL USF2 NR5A2 RALGAPA2 DDX60L ANGPT2 CSF1 FOXO1_ELF1 ATP1B1 CTCF P4HA3 DNAJC3

CREG1 ACRBP BRAT1 RHOBTB1 TEAD2 ARID5A

FBXL2 SLC12A4 SPRY4 CDC14A ATF3 ETV5_HOXA2 CHST11 GCNT1 ESM1 FZD8

IVNS1ABP MGP CROCC

SLC39A14 DUSP7 MAP2K6 TOB2 SLC35G2 SPTY2D1 BMP4 ERG ST8SIA4 POLI MCL1 SOX13 CROT

CGNL1 MXD1 ETS1 THBD BACH2 ELF1 PLAUR STC1 SGK3 ITPR2 IRAK2 PHC3 FAM198B AIM1

RNF122

ETV3

FKBP14 PIM1 MX1 TNIK MMP10

ST3GAL5 DUSP1 GULP1 INPP5A PSTPIP2 MEF2C PNP IPMK STOML1 ARHGEF18 ICOSLG MYO1E ZBTB18 PMCH MBNL3 RIOK2 TNFSF10 KITLG DHRS1 C1orf198 TMEM2 KRT80 NID2 SERP1 WNT9A PLCXD1 HBEGF PDE2A

EDEM1 STEAP1 FLT1 SDPR NEDD4L SEMA6D CLASP2

ARHGAP28 SSBP3 FBXO32 ELL2 EDIL3 ACKR3 SYNM

TFPI

XPA DOK5 HTR1B EDEM3 ZNF217 DDI2 CPEB4 SSH1 SEL1L COLQ ZNF267 RCAN1 NAB2

PDGFA

GPX8 ZBTB10 DLL4 LHX6 TSPAN13 FKBP11 PLXNA2 B4GALT5 CARS NEDD9 TMCO4 PTGER4

NANS

MYRIP CTSH

KRT19 SEPT5 DLG1

RCAN3

RNF144A MEGF6

VGLL4 CREM RFC3 HSD17B2 NFE2L2 MAFF

CD200 PLVAP PDIA4 C12orf44 ZCCHC14 CHST1

MYBL2 SLC19A2

TRIB3 RASGRP3

YRDC

RP9

SERINC5 GPR176 RNF145

AHNAK2

MCM10 KCTD12 IDH3A NR1H3 ETV5 ID3

ADAMTS9 PELO WASF3 BCL6MIDN

PLLP SETD8

ATP8B1

EFNA5

ATP8B2

NT5E

VIMP SLC41A2

HSPA5 M3: M1: PEX5 M2: Response to hydrogen peroxide response to endoplasmic reticulum stress Regulation of cellular extravasation Positive regulation of endothelial Cellular polysaccharide biosynthetic process PDGF signaling pathway cell proliferation

CCNG2

FAT1

TOX

MYO15B

ATP5H

RBPJ

CABLES2

NCAPG

TCF15

POLE4

RGCC

DHRS3

PFKFB3 ZNF143 PCIF1

ARSJ ZNF697 TBCC

FLRT2 N4BP2

ZBTB21

DPF3 NAMPTL NUP85 ZNF76 COL4A3BP PTGS2 TRIB1 GSDMD NRG1

PRKACB TM4SF18 CNKSR3

APOLD1 ITGAV LYSMD3

IL6ST ANGPTL2 IL1A TRAF1

BHLHE40 NR2F1 NDRG1 RIPK2 SLC7A5 C10orf128

SLC38A2

SERPINH1 C8orf4 B3GNT5 CSRNP1

GADD45A

TPP2

MFSD6

RAPGEF5 PALLD USP53 CREB5 CXCL2 SLC26A4 MDM2 C10orf10 B4GALT4 COL8A1

CXCL1 ZEB2 POLR3D IL8

NYNRIN IFRD1

SIK1 PDE3A SLC10A7 GABPA PER1 BIRC3 NFKB2 SMAD3 ZNF704

TIPARP

TLE4 PDE4D SAT1 GARS RPS6KA1

GPR126 FOXO1_ELK1 ATP2A2

MN1 NOS3

GBP1

RUNX1 FOXO1_ETV1 PITPNC1 NUCB2 MEX3C

PKIG BMX ITGB3 FOSL1 MYL4 DKK1 ZC3H12A TSHZ1 HMGN4 IRF2 TNFSF15

AQP1

CRELD2 NF1GATA3 ANK3

CCL2

TSC22D4 BBC3 LIPG SOX4 ETV5_FOXO1ERF_FOXO1 RARG HDAC5 HK2 SLC7A1 HIVEP2 JUN TMEM173 JUN-AP1 FOSL2 ABCC4

CLDN11 DIP2C NOG MOSPD2 GCH1 CD40 TSC22D2

FOSB LARP1B

PIK3R1 GPRC5A SETX ATF1

EIF2B3 PALD1

FOXO1_ETV4 FARS2 HSPA13

TBX18 KCNN3

KLF4 HHIP GNG2

IL1RL1 PARP12 FAM124B ELK4 XBP1 PTX3 THSD1 SERTAD3

STC2 IDI1 ALDH1A1 RAB3B SERPINE1

TRIB2 VCAM1 SELE

ITGB8

SLC9A3R2 FOXO1CHST3 GDF6 CCL20

MTHFD2

RND3 MEF2A SLC12A2

GCOM1

A2M STARD4 GATA6 CAMK2N1 IL33 RNF144B HERPUD1

DTNB

SDC4 YPEL2 SOD2 IL6

FOXF1 ZC3H12C LAMP3 ADTRP DCBLD2

SLC30A7

ZFAND2A PJA2

TSPAN5 SLC33A1

IRS2

SGK1 UGDH NRG3

CXCL3

FAM185A

MIS12

SLC30A1

RELB PCDH12 ALAD

PPIL4

SEMA6C IL27RA

CIC

ICAM1

PPP1R15A M4: M5: ADAMTS1 M6: Positive regulation of cytokine secretion Nitric oxide metabolic process Muscle cell proliferation; Negative regulation of endothelial cell migration Regulation of muscle adaptation Positive regulation of leukocyte migration

MAFG B C 20 D 15 VEGF 10

HPAEC HUVEC ECFC HMVEC FPKM 5 0H 1H 4H 12H MAFF 0 MAFF H0 H1 H4 H12 MAFG MAFG MAFK 10 MAFK 8 MAFK 6 Tubulin Tubulin 4 FPKM 2 0 H0 H1 H4 H12

150 MAFF

100

FPKM 50

0 H0 H1 H4 H12

Supplemental Fig. S7. MAFs are master regulators of VEGF transcriptional network. (A) Sub-networks from Fig. 7B. The VEGFA regulatory network contained six major sub-modules showing diverse functions. (B). Western-Blot detecting MAFs expression in four different types of ECs. HPAEC: human pulmonary artery endothelial cell; HUVEC: human umbilical vein endothelial cell; ECFC: endothelial clone forming cell, HMVEC: human dermal microvascular Endothelial cell. (C) VEGFA upregulated expression of MAF factors at H1, as revealed by RNA-seq. (D) VEGFA upregulat- ed the expression of MAF at H1, as revealed by western-blot.