Nature Medicine doi: /nm.2772

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22 Supplementary Table 1: FOXO3a and/or beta catenin regulated genes (12 h treatment) FC 4OHT FC DOX FC 4OHT+DOX FC 4OHT+DOX Known Gene Symbol vs. Vehicle P value* vs. Vehicle P value* vs. Vehicle P value* vs. 4OHT Target SLC2A ANKRD E E E FSIP2 n.s. n.s SLC1A E 04 n.s E C10orf n.s MCOLN IQGAP E E TMPRSS11F n.s LCA CPA4 n.s CYP24A n.s KTN RB1CC CD2AP LOC RIMKLB FRMD6 n.s KRT n.s JMJD1C n.s NIPBL HSPA4L E CLEC2B n.s DAB EMP (b) NAV ARHGAP E E BMPR1B CCDC KLHL n.s GPR RARB n.s INPP4B RECQL HIST1H2AL n.s PIK3CA n.s E (b) GBP3 n.s MPP5 n.s GOLGB n.s NCRNA n.s ACTA PNPLA n.s NSAP E 06 n.s E PRDM E KLHL KRTAP NT5E n.s E C13orf LPHN E 06 n.s E WWC CTNNAL FRYL n.s GOPC n.s E ATP13A PLK E CLDN E DCP HNMT n.s E RICTOR n.s ARHGAP n.s

23 STAMBPL CFTR FCHO n.s HIPK E KRTAP SGTB n.s L3MBTL E E SLC7A E E CLDN n.s DAAM n.s RASA n.s VSNL n.s CTGF E E RAB3B n.s E NEIL n.s HBEGF n.s E MBNL n.s TMEM ALS2CR n.s YOD WDR n.s XRN n.s TFPI E E PFDN n.s TBC1D PDLIM STARD n.s SPTLC E CRIM n.s RAB KRTAP TEAD GCNT E E UTRN E HAPLN n.s PCMTD HEG E POC1B FMNL IMPA FBXO n.s HEATR5B n.s ITGA ARHGAP NFE2L n.s NDFIP n.s CAV OSGIN E CDC14A E E (b) STK17A CRIPT n.s FEM1C E SEPP E E TSPAN n.s PLEKHA LGR n.s (a) E2F n.s KRTAP3 1 n.s E RP n.s IL n.s SNORD73A n.s CD n.s GDA n.s E

24 CHIC n.s SYNE n.s ZNF n.s SLC28A E 04 n.s E UBE2D E 04 n.s E CAV E E (b) RALGPS E 04 n.s E CYP39A n.s YPEL ABCA E 09 n.s E CRY TJP JPH n.s PTPN ERV n.s DOCK TOR1AIP LGALS n.s E CHMP4C n.s CCDC RBMS n.s RIOK E E RAET1L n.s SERPINB n.s (b) TIMP (b) TES E E RNF FAM134B E 06 n.s E UBN E E TMX n.s SESN E E CLK USP RGL n.s PMAIP E E WHAMM n.s PLCE n.s ODZ n.s CYBRD E E SAV n.s GFPT DOCK SNAP n.s HIST1H2BM n.s XK ZFAND n.s ITGB n.s ARNTL PPFIBP NETO n.s TTPA DUSP (b) BRD n.s GPR137B n.s GAB TLR n.s BAG (a) SWAP n.s PARD6B n.s E DOCK n.s E UBL n.s PAWR TGFBR

25 ERO1LB n.s TGFA n.s (b) SLC1A E E SOS n.s PIM n.s KLF n.s TNFRSF n.s (b) AFF E 04 n.s E AVIL n.s SNORD BMP ANK n.s RRS n.s TM4SF E TRIP n.s POLR1B E E (a) THBS SEMA3C n.s (b) RTN n.s CLTB ZFAND IL22RA n.s C1orf n.s KLF E 04 n.s E (b) HSD17B E E NEDD4L n.s (b) CDKN1B n.s (c) ARID5B (a) RNF MAGI n.s SLC31A E 05 n.s E (b) GADD45B TRAK n.s CORO1A (b) KLF n.s GPR TGFBR n.s ABLIM n.s JAK CYR E E (b) CCNG (b)(c) C18orf n.s KLK (b) CDKN2B n.s FOXP E E LIPG GATS SNORD MTNR1A CDCA (a) LDLR E 04 n.s E ABHD n.s SAT TSC n.s ERRFI n.s NPIPL n.s NCS ATXN E E TCF n.s ATL E E FAM27E n.s KIT SRGAP n.s

26 CENPP TNS n.s GLUL n.s SH3TC n.s SMPDL3A (b) ZRANB CITED E E HECA n.s STX UBE2H (b) ATP8A E 04 n.s E EGR E E SNX n.s EDN (b) PIGM n.s PDIA DDI n.s EIF2C n.s ARHGEF E 04 n.s E NT5C n.s DPYSL IL1F E E LIPH FMO TMEM E 04 n.s E CYB5RL n.s TSR SLC12A E 04 n.s E DUSP E E (b) GEMIN n.s (a) BRAP n.s TMEM200A n.s WIPI RRP1B n.s FCHSD n.s C10orf n.s PTPRJ E 05 n.s E NOP n.s BCAS WDFY n.s ACPP TMEM n.s EFNA n.s NPC n.s RRP n.s NDP MACF n.s TDRD OPTN RASGRP CDCA7L FKBP POLR1A n.s BYSL n.s (a) CTH USP ARL2BP SLC5A n.s TMEM86A MXI E 04 n.s E (b) SASH n.s SCIN E 07 n.s E RAB5B

27 NPNT n.s FAM59A n.s LRP E E CTSB E (b) S100A n.s (b) OR7E87P PSMG n.s GRIK NTAN E 04 n.s E SQLE TIMM8B n.s E SORL E E PPP1R15A MRPL n.s B4GALNT n.s FOXO n.s MAML PYCR n.s C10orf n.s MRPL n.s DSP NME n.s UCA RAB9A n.s NRM GPLD n.s PELI MAOB E E SLC4A FOSL E 04 n.s E TBC1D E E CHMP4B E 05 n.s E GATSL KIF13B n.s CTDSP ATP9A NECAP n.s RERE E (b) LGR E 04 n.s E EGLN n.s SUN n.s ARRDC E E TRIM n.s AIMP E FGF E 04 n.s E ZFHX LY6G6C n.s PRR MFSD SLC29A n.s C8orf n.s MTSS1L TGFB PAQR n.s S100P n.s (b) IRS E 06 n.s E EPHX n.s REXO E 05 n.s E MAST DNMBP SCD n.s (a) SLC2A n.s CCDC

28 BTG n.s (c) ANP32A n.s PLXNB n.s MBTPS SPINK E PDK MEGF E 04 n.s TST (b) HBP BCL E E (b)(c) AKAP n.s BTG n.s NFIC n.s NDRG E E IPO n.s BACH E 05 n.s E IGF1R n.s (b) SLC16A n.s KIF3C (b) C17orf n.s SLC6A TMEM161A TNFSF E E (c) GYLTL1B n.s BOD n.s KPNA E 05 n.s E SNORD CARS n.s TMEM E EPB41L n.s TTLL n.s FOXO TEP n.s CYTH C19orf n.s ZFYVE E 04 n.s GMPR GAB E CHD n.s SLC19A n.s (a) NDUFV ERBB E E (b) RNF LNX E IGFL E WDR n.s (a) TNRC SLC16A GTPBP n.s TUBA1A n.s IER E 05 n.s CBLB TMEM n.s AMPD (a) GRB E (b) HES SLC2A n.s RNF n.s TMEM E 06 n.s E SLC44A ATG2A TIGD n.s TRERF

29 SLC45A n.s SOBP n.s PPAP2B E E RNF IL10RA n.s CCL PNPLA INSIG E ARHGAP n.s GTF2I n.s (b) VAMP LAD n.s PIK3IP E 04 n.s SH3RF n.s INSR E 04 n.s ZNRF n.s (a) RAB MPI TCP11L E E CARHSP E MID1IP E YPEL CABLES n.s EPN ULK SLC43A E ZNF n.s GSN (b) PPFIBP TNS n.s MED n.s FASN CALCOCO LAMC REPS SCNN1B n.s TMCC REG n.s THOC CA5B n.s TLCD DBP E PLCG E 05 n.s E (b) PIK3C2B C10orf E 05 n.s E SGSH NDUFB FBXO E 04 n.s E (c) PDZK1IP TP53INP SULT2B ID (a) STARD ZNF n.s SLC1A (b) LFNG n.s TNFRSF EFNA DGCR ZNF n.s DAPK E (b) TNFSF SERPIND

30 GPR SOD (c) SLC22A n.s HSD17B n.s PRR15L ASCL E (a) KRTAP CDX SULT1C E TXNIP TRIM RND E DHRS TMOD n.s PLA2G2F n.s Supplementary Table 1. High Stringency Gene List of Genes Regulated at 12 h Treatment. The results of the microarray analysis were cut off at a significance level of Bonferroni adjusted P value (asterisk) 0.05 (corresponding to a false discovery rate (FDR) P value ) and a fold change (FC) of at least two fold in at least one of the treatments. The fold change is displayed as value in treated cells versus value in control cells (vehicle). n.s. = not significant in a two tailed ANOVA analysis (P value > 0.05). The list is sorted indicating first the highest fold change value for double treatment (4OHT+DOX) versus 4OHT. Known target genes were previously described: (a) gene found to be regulated by N TCF (van der Flier et al., 2007); (b) FoxO3a target gene described by Delpuech et al., 2007 and (c) summarized by Greer and Brunet, 2005.

31 Supplementary Table 2: FOXO3a and/or beta catenin regulated genes (24 h treatment) 4OHT DOX 4OHT+DOX FC 4OHT+DOX Known Gene Symbol FC P value* FC P value* FC P value* vs. 4OHT Target SLC2A E SLC1A n.s KRTAP n.s CPA E E E ANKRD E E E DAB E IQGAP E E RTKN KRTAP n.s CLDN n.s WWC DEPDC n.s KIF18A n.s DIAPH PRDM E SEMA5A LPHN n.s MS4A n.s SPINK E ULBP n.s CLDN n.s ARHGAP11A n.s KRTAP C13orf CLEC2D n.s SLC31A (b) STARD PHLDB BRCA n.s SLC28A n.s E ATAD n.s NSAP n.s SLC45A E 04 n.s E SDR16C n.s EMP E (b) PSG n.s JMJD1C n.s HEG E CP n.s SELP E 04 n.s E AMOTL E EDN E E (b) PUS7L n.s ZBED n.s AXL n.s NAV REEP n.s VSIG PIK3CA n.s E (b) C4orf n.s RIMKLB SKIL n.s NPIPL n.s E DUT MAGI n.s TNC GCNT E RAB3B n.s ANLN

32 HAUS n.s MIR RAD51AP n.s CTGF E E COL10A n.s DSCC ABCA E 05 n.s E STX RARB n.s FCER1A n.s NBEAL PSG n.s XG n.s WDHD E 04 n.s SASH n.s PLK E MMP n.s RICTOR n.s CCDC n.s IL1F E E GADD45B NTAN n.s MALT KIF LAMA n.s DEPDC1B n.s GPRC5A MAP E TINAGL E CLIC n.s TBC1D YOD KPNA E E C21orf n.s E CTNNAL RAB n.s SEMA3A n.s TIMELESS n.s GREB n.s E FGD n.s ARHGAP FBXO (c) WDR n.s ZDHHC NTN n.s C6orf n.s SCML ZSWIM n.s TNFAIP TFPI n.s CSRNP LY6G6E n.s MPHOSPH n.s MBNL n.s FOS CCDC CHN n.s HELLS CDKN2B EIF1AY n.s MAML FCHSD n.s TUFT n.s

33 TBC1D n.s E TMEM E E CGA n.s TEK n.s SLC7A E E RAD n.s CSGALNACT n.s SYNE NEBL n.s PTPRR n.s FYN E GTSE n.s TMSB4X n.s CYR E E (b) FRYL n.s RGL E AMIGO SLC1A TTC n.s NT5E n.s DOCK SERPINB (b) PYGL CRIM E SECISBP2L n.s FBXO n.s E FANCA n.s XRN n.s RALGPS E E ALS2CR PLOD E E CEP NOC3L E (a) TEAD BLM n.s MCTP E E C5orf E BACH OSGIN n.s DAAM n.s PRC n.s (b) CLTB ELOVL n.s CEP n.s GULP n.s VILL n.s SLC30A n.s DUSP n.s HBEGF n.s CYTL n.s UBE2B n.s SYNJ n.s RAD L3MBTL n.s E ABTB n.s E TIMP n.s (b) PMAIP n.s PHACTR n.s BAMBI n.s ATL PBK n.s RAB5A n.s PEX n.s

34 CLDN FCHO HIST1H1B n.s ZNF E 04 n.s E ITGB n.s WDFY E FABP SCIN E 04 n.s E MARCH n.s HECA n.s GTF2B n.s PIK3AP CTSL POC1B TMSL n.s ATP6V1E n.s CYB5R KIF n.s (b) CYTH n.s AURKA n.s (b) RAB4B n.s E INPP4B n.s DDX CAV E E (b) POLH n.s MFGE E 04 n.s E RASA n.s TRAM n.s SLC7A E (b) NUSAP n.s IL n.s E CA5B E XPO n.s PLEKHA n.s MMD HIST2H3A n.s DNAJB PPP2CB CAV HIST1H4K E PHGDH C11orf n.s APLF n.s PARD6B n.s SESTD n.s TIMP n.s GSG BUB E 04 n.s CHEK NKD SLC7A E (a) HAPLN n.s FANK n.s EZH MSH SYTL n.s RNF n.s CHMP4C n.s SLC2A MXI n.s (b) PAWR n.s TCF AURKB (a)

35 SKA n.s PIK3IP n.s SHCBP n.s OBFC2A n.s ODZ E E RFC n.s SNHG n.s STXBP UBE2C (b) EIF2C UPK3B SUV39H n.s WDR n.s (b) PDLIM MRPS n.s SESN ATG2A NEK n.s (b) BACH E 04 n.s E TSPAN UBE2D n.s CDC14A E E (b) INTS n.s CDKN1A n.s (c) PCMTD MXRA n.s SCARA SSFA n.s TRAK CHRNB RAD54L n.s RIOK n.s RAD51C n.s SNORD4A n.s UTP RTN n.s TDRD UCHL E RAET1L DDX (a) LMO n.s CYTH n.s UCK n.s NAV GFPT n.s RNF n.s SNAP E 05 n.s E IRF CHIC E 04 n.s E RSPH n.s TES E E PPIH NOL NUDT E E SPAG n.s XPR n.s SWAP n.s SEC14L n.s AFF E 05 n.s E ZYX HIST1H2BM n.s OSGEPL n.s RFC

36 HIVEP E C15orf SP KLF n.s ZFHX TJP n.s TMOD n.s MBNL n.s RANBP B4GALNT CCNG (b)(c) PTPN E E EPS8L n.s TROAP MAP1LC3B E PTPN n.s E CDCA CYP39A E E NDRG E E SMURF n.s OR2A20P E 05 n.s E KDELC n.s AGR E SLC29A n.s FLJ DOCK n.s SNORD ZFYVE E E WDTC ACVR1C n.s NUP n.s CR SEMA3C (b) ZBTB n.s FANCC n.s FOXM (b) NECAP n.s WWTR n.s SLC1A n.s CCDC PTPN CHMP n.s PPFIBP n.s ILDR ETHE ATP8A NCAPD E 04 n.s GATA n.s PDGFRL TCP11L TMEM E 06 n.s E TNS n.s SMC1A E SHROOM E E RAB9A n.s CD E 04 n.s E IL2RG E 04 n.s E LDLR ARID5B E (a) TCF n.s GATSL E E ITGA n.s CD (b)

37 TMPO n.s RACGAP n.s FANCG MCM E ANXA ABLIM n.s PIK3C n.s SLC12A SUN E 05 n.s E BACE POLB E KLHL SNX n.s NAPG POLD MEGF GBE n.s GM2A (b) SLC4A n.s DCAF CRIPT n.s WDSUB n.s NSUN5P ZFAND n.s HIST1H3I n.s REEP n.s KIF18B E E C9orf n.s ERV HADH n.s QPCTL n.s SKP n.s RRM n.s CBLB CALCOCO SPTB ZFAND E E STX ICK E E RCCD ARHGEF n.s REPS CALHM n.s RBMS MTO SPTAN TP n.s TSR E PC n.s CXCL n.s (a) LASS C1orf KIF3C (b) TMEM86A KLF NDUFV n.s GAB n.s TYMS n.s TNFRSF E E (b) TEP CCDC n.s E2F n.s ANAPC n.s

38 SEPP E E ACPP E OPTN n.s BCL (b)(c) TGFBR n.s FEN n.s RCAN TUBA1A n.s STRADB E E LASS n.s GDA n.s SAT E E TOR1AIP n.s NAF LAMC RYBP n.s YIPF FRMD n.s OTUD n.s PTPRG E E MAGI n.s NT5C n.s JAK E E GMDS n.s NUP n.s LY6G6C E E FOXP E E C7orf n.s CYBRD E 04 n.s E ARHGEF E 04 n.s E IPO n.s PRSS n.s TTF n.s PPAT TRMU n.s XRCC6BP n.s LRRC8A PINX n.s NCAPH ESPL POU5F n.s FMNL n.s NHLRC PNRC YPEL URB n.s UCA n.s DDI KIAA n.s ATXN n.s BTG n.s (c) TIPARP n.s CYTH n.s RAB ANGPT E 04 n.s E BMPR VEPH n.s ARHGAP n.s HSD17B n.s FOXO E E RHOF IGFBP GEMIN (a)

39 ABHD n.s TPRA E 04 n.s E FADS HSPE n.s FLNB n.s E TUBG n.s SLC5A n.s BUB1B n.s VAMP n.s PDSS KLF n.s (b) PRR MACF E 04 n.s E DNMT n.s NOP n.s RNFT n.s RND n.s NEDD4L n.s (b) PIGW n.s (a) DTL n.s GPR137B n.s CDC n.s RRP SERINC n.s PHF21A PIK3CB n.s PDZK1IP PPP1R15A PDIA E E HSPA4L n.s MAP4K n.s CCNDBP GATS LGR n.s SOD n.s (c) TRIM FOSL E 04 n.s E KIF20A E E TSPAN E E FGF E 04 n.s E MCM n.s CITED n.s C10orf n.s LRP SLC2A E 05 n.s E SLC35D ITGAX TCOF ERBB E E (b) ARRDC E E DPYSL E 05 n.s E CENPM E 05 n.s E RERE n.s (b) TGFA n.s (b) FAM64A n.s EPRS n.s LGMN TMCC E SRM (a) ABI n.s GPX n.s LGR n.s (a) DUSP E (b)

40 PLK SFMBT n.s FARSB n.s IARS n.s (b) CD OR2A n.s GALNT n.s TM4SF E E TTC SUPT16H n.s PTTG1IP n.s OR2A n.s PSRC E2F n.s SHMT n.s RBMX n.s ZNF n.s SPAG SNORA CRTAM TGFBR TBC1D n.s XPO TRNP n.s ITGB CAD n.s (a) PAK1IP DUSP E E (b) CTSB E 04 n.s E (b) IRS E 05 n.s E DHRS n.s ERRFI E E EGLN SCFD n.s ACY COL17A C10orf APCDD n.s UCP CYP2S E E PPIF E (a) TNS E E CGREF n.s HLA E n.s UBE2H n.s (b) GPRC6A KCTD E E PPAP2B E SLC2A PSMG n.s BAG n.s (a) SLC43A E 04 n.s E PYCR RPL27A n.s GDF MDC n.s PXK n.s CASZ HSPG NUCKS n.s TMEM NAT n.s GPR

41 KIFC n.s PLAT n.s ATP5G n.s MAST ACACA n.s CAMK2N MMACHC n.s WRB n.s AKAP n.s TOE n.s E USP HNMT C5orf n.s LEF E 04 n.s E (a) NR6A n.s TNRC MRPS n.s SORL TNFSF E E (c) MRGPRX E E TARBP n.s C19orf n.s CARS n.s CLIC TRIP n.s UCK n.s ANGEL n.s NUP n.s PCDH PRPF n.s KLK n.s (b) SREBF STEAP SERPINE E E RRP1B ATP9A E E EPHX S100P E 05 n.s E (b) RAB11FIP GEMIN E E (a) CAB39L TP53INP E E NLE n.s (a) ITLN n.s TOMM40L WDR n.s OAS LIPH IL10RA E 05 n.s E MRPL n.s (a) GRB (b) DKC n.s (a) ITM2B NFX n.s GLUL E E DLEU n.s FSTL E 04 n.s E MAOB E 05 n.s E PRMT n.s THBS E E ILF n.s WDR (a) SLC1A E E (b)

42 NBEAL n.s HES KIF13B n.s AADAT n.s CCDC n.s WDR n.s CLU n.s (b) TNFRSF EGFR n.s SF3B n.s PLBD AFF ABHD ASF1A n.s KSR n.s CDC42EP n.s (b) GPI n.s NRM n.s E DCAKD n.s RAG1AP MAZ ZMYM SLC16A n.s MLEC n.s TUBA4A n.s AFAP n.s E SLCO4A n.s TSPAN E E E KIF2C n.s UTP FRRS n.s MT1X n.s SLC44A MAGT MANEAL n.s E PCYOX1L n.s UTP14A LRRC37A LGALS3BP PA2G E 05 n.s E GNL n.s AIMP n.s CDK n.s (a) MRPL n.s IGF1R E E (b) PLCE n.s E PRKAR2A ARHGAP E 04 n.s GSN (b) CTTNBP n.s CD (b) HGSNAT CLDN (a) HSD17B n.s CRAT E E SCARB n.s TNS COQ MID1IP n.s ATP1B LPHN n.s MOBKL2B n.s APRT

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