A Family GenBank Ref Pseudo repFamily repClass repName Ref HERV_H AJ289711.1 Laska and al, 2012 ENV59 LTR ERV1 HERVH-int AJ289710.2 ENV60 LTR ERV1 HERVH-int AJ289709.1 ENV62 LTR ERV1 HERVH-int Jern and al, 2005 Pol62 LTR ERV1 HERVH-int HERV_K (HML-2) LTR AF333072.2 Tai and al, 2008 K18 ERV1 HERVK-int AF164610.1 LTR HERVK-int Christensen, 2005 K102 ERV1 HERV_W AF072506.2 Mameli and al, 2007 ERVWE1 HERV17-int/LTR17 ERV1 HERVW-int B Digital dropplet PCR 160 8 140 7 Jurkat cells (near diploid) 120 6 HAP1 cells (haploid) 100 5 80 4 60 3 40 2 20 1 DNA copy number per chromosome 0 0 env env env env env LTR pol LTR Sat2 fos IL8 59 60 102 62 62 62 18 - TNF c chr11 FOSB TGFb1 H K W H K RPLP0 HERV HERV Promoters H7 K20 C BpV(pic) 8 Vehicle D 90 Vehicle ** 30' *** ** 30' 60' 6 60' 60 ** *** 4 *** * *** ** *** * 30 and RPLP0 and RPLP0 2 *** *** 0 0 TGFβ env59 env60 env62 pol62 LTR-K18 env-K102 env TNF IL8 Fold change in RNA levels relative to vehicle Fold change in RNA Fold change in RNA levels relative to vehicle Fold change in RNA Control HERV_H HERV_K HERV_W Cytokines Figure S1 E Live cells/mL Dead cells % DMSO 1h 87.104 0% Dieldrin in DMSO 30 min. 85.104 0% Dieldrin in DMSO 1h 92.104 2% Vehicle F 8 Dieldrin * 30' C 7 60' 6 5 4 3 RPLP0 2 1 0 CYP1A1 CYP1B1 NQO1 GCLC GCLM SLC6A12 SLC5A3 AKR1B1 H2AFX CDKN1A MDM2 BAX VEGF DNAJB9 MT1E MT2A HSP90B1 HSPA6 Fold change in RNA levelsrelative to vehicle and Fold change in RNA Environmental Oxidative stress Osmotic stress DNA damage Hypoxia ER stress Metal Stress Heat Shock stress G 8 Vehicle PMA 30' 7 60' 6 ** 5 4 3 RPLP0 2 1 0 CYP1A1 CYP1B1 NQO1 GCLC GCLM SLC6A12 SLC5A3 AKR1B1 H2AFX CDKN1A MDM2 BAX VEGF DNAJB9 MT1E MT2A HSP90B1 HSPA6 Fold change in RNA levels relative to vehicle and Fold change in RNA Environmental Oxidative stress Osmotic stress DNA damage Hypoxia ER stress Metal Stress Heat Shock stress Figure S1 H DAPI TRIM28S584p HP1γ DMSO Dieldrin Camptotecin 2μ Figure S1 A DMSO Dieldrin PMA B DMSO 30' 60000 Dieldrin 30' PMA 30' 50000 40000 30000 20000 10000 0 T68 T60 S46 S15 S63 Y411 Y411 T183 T308 T172 T389 T246 T198 S392 S473 S133 Y419 Y397 Y394 Y689 Y694 Y397 Y751 S727 Y402 Y420 Y426 Y412 Y641 Y699 Y705 Y783 S1177 S1177 Y1086 S2448 S21/S9 S78/S82 T180/Y182 T421/S424 S376/S360 Y694/Y699 S380/S386/S377 T202/Y204, T185/Y187 T202/Y204, T221/Y223 T183/Y185, Ref Spot p38 ERK1/2 JNK1/2/3 GSK3 α/β p53 Ref Spot EGFR MSK1/2 AMPK α1 Akt 1/2/3 Akt 1/2/3 p53 TOR CREB HSP27 AMPK α2 β Catenin p70 S6 p53 c-jun Src Lyn Lck STAT2 STAT5a p70 S6 RSK 1/2/3 eNos Hck ChK2 FAK PDGF Rβ STAT 5a/b STAT3 WNK1 PYK2 Ref Spot PRAS 40 HSP60 Fyn Yes Fgr STAT6 STAT5b STAT3 p27 PLC-γ1 kinase kinase C HERV_H_env62 D TNF E C-jun F FosB G cFos *** 4 600 250 90 ** ** 3 40 200 400 60 150 2 20 100 200 1 30 50 vehicle and RPLP0 vehicle and RPLP0 vehicle and RPLP0 vehicle andRPLP0 vehicle and RPLP0 0 PD98059 0 PD98059 0 PD98059 0 PD98059 0 PD98059 Fold change in RNA levels relative to Fold change in RNA Fold change in RNA levels relative to Fold change inRNA levelsrelative to Fold changein RNA Fold change in RNA levels relative to Fold change in RNA Fold change in RNA levelsrelative to Fold changein RNA Vehicle Dieldrin Vehicle Dieldrin Vehicle Dieldrin Vehicle Dieldrin Vehicle Dieldrin Figure S2 A Dimethylation of H3K9 B Vehicle 4,0 BIX treatment 16h Vehicle 3,0 0,1 µM 0,1 µM 1 µM 1 µM 3,0 10 µM 10 µM 2,0 ** ** 2,0 ** 1,0 and RPLP0 and RPLP0 1,0 0,0 0,0 TGFβ env59 env60 env62 pol62 LTR-K18 env-K102 env Sat2 TNF IL8 Fold change in mRNA levels relatiftovehicle Fold changein mRNA Fold change in mRNA levels relatif tovehicle Foldchange in mRNA Control HERV_H HERV_K HERV_W Satellite Cytokines C DNA methylation D H19 locus Azadesoxycitidine treatment 16h 40" *** Vehicle 6,0 Vehicle 15,0 0,1 µM H19$$ 0,1 µM 1 µM 40" 1 µM 10 µM 30" 10 µM 4,0 10,0 * 30" 20" 20" ** C(t)" 2,0 5,0 C(t)" and RPLP0 and RPLP0 10" 10" 0,0 0" 0" 0,0 TGFβ env59 env60 env62 pol62 LTR-K18 env-K102 env Sat2 '" TNF IL8 Fold change in mRNA levelsrelatifvehicle to Fold change in mRNA Fold change in mRNA levels relatif tovehicle Foldchange in mRNA '" Control HERV_H HERV_K HERV_W Satellite Cytokines 1"μM" 0,1"μM" 10"μM" 1"μM" 0,1"μM" 10"μM" E DNA methylation F Trimethylation of H3K9 Azadesoxycitidine treatment 16h Chaetocin treatment 0.1μM 15 Vehicle * 25 0,1 µM Vehicle * 30' 1 µM ** 60' 10 µM 20 240' 16h 10 15 * * * ** 10 5 RPLP0 and RPLP0 ** 5 0 0 TNF IL8 Fold change in RNA levels relativeto vehicle and Fold changein RNA Fold change in RNA levels relativeto vehicle Fold change in RNA TGFß c-jun c-fos FosB Cytokines Figure S3 A B TNFAIP6 12 CD83 12 B *** *** 9 9 *** 6 6 *** RPLP0 ** RPLP0 *** 3 *** 3 *** 0 0 - 30' 60' - 30' 60' - 30' 60' - 30' 60' Fold change in RNA levels relative to vehicle and Fold change in RNA Dieldrin PMA levels relative to vehicleand Fold change in RNA Dieldrin PMA C Table showing values for repressed genes mentioned in the text D Panel showing that when reads with 20As overlap with HERVs, their A tract is mostly encoded by the geneome. Figure S4 A HERVd annotation assembles HERVs fragmented in RepeatMasker : example B Divergent transcription Divergent transcription Dieldrin DMSO HERVd FOS ENCODE TF C D Dieldrin Divergent transcription activated by dieldrin DMSO Divergent transcription activated by dieldrin HERVd CLHC1 Dieldrin ENCODE DMSO TF HMGCR HERVd E GO Biol. Process. on genes in proximity of HERVs showing divergent transcription activated at least 2-fold by dieldrin Figure S5 F Example of a transcription factor gene in HERV-free zone: MYC. Note the increased elongation in the presence of dieldrin. DMSO End of promoter transcription End of transcription Dieldrin Last HERV First HERV RepMa MYC HERVd G Distribution of HERV densities in transcription factor genes and other genes (in %) Figure S5.