Supplementary Table S3

SKN-1-dependent upregulated genes under reduced IIS (ranked by SAM score)

SAM Rank Public Name KOG (euKaryotic Orthologous Group) Title Score(d)1 F55G11.2 similar to human Epoxide hydrolase 1; RNAi lifespan variant 6.4052 col-13 Collagens (type IV and type XIII), and related proteins 4.7873 K10H10.4 oogenesis,cuticule 4.3974 K10C2.3 Aspartyl protease 4.116

5 K04C2.5 RNAi results in larval lethal 4.0326 nas-7 Meprin A metalloprotease 3.9877 col-127 Collagens (type IV and type XIII), and related proteins 3.946

8 nit-1 Carbon-nitrogen hydrolase 3.7859 dct-5 DAF-16/FOXO Controlled, germline Tumor affecting 3.727

10 F56D5.3 NADH:flavin oxidoreductase/12-oxophytodienoate reductase 3.72611 C32H11.4 similar to human Epoxide hydrolase 1 3.712 pgp-7 Multidrug/pheromone exporter, ABC superfamily 3.58613 F29G6.1 similar to human Follistatin; RNAi results in embryonic lethal 3.54314 T10E9.3 contains DOMON domain (DOpamine beta-MOnooxygenase N-terminal) 3.54115 nspb-7 Nematode Specific Peptide family, group B 3.505

16 col-66 similar to human Pulmonary surfactant-associated protein D 3.3717 col-12 Collagens (type IV and type XIII), and related proteins 3.35518 col-146 Collagens (type IV and type XIII), and related proteins 3.338

19 str-180 7-transmembrane olfactory receptor 3.33720 C06G1.1 BPI/LBP/CETP family protein 3.32521 F39D8.3 Unnamed protein 3.30422 F53B3.3 Uncharacterized protein 3.29823 col-176 Collagens (type IV and type XIII), and related proteins 3.28924 Y70D2A.1 7 transmembrane receptor; similar to human G-protein coupled receptor 139 3.28225 C28D4.4 contain domain of unknown function (DUF1248) 3.27826 col-65 Collagens (type IV and type XIII), and related proteins 3.277

27 dod-24 3.26628 tyr-2 Predicted tyrosinase 3.24329 C06E8.5 Lipid-binding serum glycoprotein motif 3.2430 col-133 Collagens (type IV and type XIII), and related proteins; RNAi results in embryonic lethality 3.234

31 grd-6 3.217

32 ptr-23 3.18933 T21D11.1 Gelatinase A and related matrix metalloproteases 3.13334 gst-4 Glutathione S-transferase; RNAi hypersensitive to oxidative stress 3.11235 C54D10.10 predicted serine-type endopeptidase inhibitor activity 3.09636 T06A1.5 Extracellular protein with conserved cysteines 3.09337 ssq-4 Sperm-Specific family, class Q; similar to human Elastin isoform 2 3.07238 Y113G7B.12 predicted Reverse transcriptase 3.011

39 D1044.2 2.992

40 nspa-8 Nematode Specific Peptide family, group A 2.98441 col-60 Collagens (type IV and type XIII), and related proteins 2.98342 srx-58 7-transmembrane receptor 2.981

Downstream Of DAF-16; RNAi lifespan variant Murphy 2003

GROUND domains (extracellular cysteine-containing domain sometimes associated with HOG domains)Predicted membrane protein with sterol sensing domain (patched superfamily); required for molting, shortened lifespan by RNAi

EGF-like calcium binding, Nidogen, extracellular domain; RNAi affects axon guidance (Schmitz..hutter 2007)

43 F36H9.2 Unnamed protein 2.95144 F48G7.5 Secreted surface protein 2.94445 trx-3 Thioredoxin, nucleoredoxin and related proteins 2.93446 ssq-3 Unnamed protein 2.92747 C32H11.3 similar to human Epoxide hydrolase 1 2.893

48 nas-1 Meprin A metalloprotease 2.86749 dgk-2 Diacylglycerol kinase 2.85250 col-120 Collagens (type IV and type XIII), and related proteins 2.849

51 T02B5.3 2.8452 ifp-1 Nuclear envelope protein lamin, intermediate filament superfamily 2.83553 C07A4.3 2.81754 W01A8.6 2.80255 C05E7.2 Unnamed protein 2.79856 F41F3.8 2.79857 gst-12 Glutathione S-transferase 2.77458 T28C12.6 2.741

59 Y47D7A.13 2.73360 col-141 Collagens (type IV and type XIII), and related proteins 2.72261 abu-8 Uncharacterized protein 2.6562 B0334.13 2.64963 col-162 Collagens (type IV and type XIII), and related proteins 2.64464 ptr-20 Predicted membrane protein (patched superfamily) 2.63565 asm-2 Acid sphingomyelinase and PHM5 phosphate metabolism protein 2.63466 col-180 Collagens (type IV and type XIII), and related proteins 2.62367 dod-17 2.62268 col-144 Collagens (type IV and type XIII), and related proteins 2.61

69 F35B3.4 Fibronectin 2.60770 abu-4 2.60771 ttr-14 Uncharacterized protein with conserved cysteine 2.60472 F14D7.6 Predicted transporter/transmembrane protein 2.59173 col-115 Collagens (type IV and type XIII), and related proteins 2.58974 F57A10.2 VAMP-associated protein involved in inositol metabolism 2.58175 F16F9.4 Arylacetamide deacetylase 2.57976 col-88 Collagens (type IV and type XIII), and related proteins 2.555

77 C30H6.5 2.55478 col-7 Collagens (type IV and type XIII), and related proteins 2.5579 C17C3.3 Acyl-CoA thioesterase 2.55

80 cutl-23 Cuticulin precursor 2.54981 F10D11.6 BPI/LBP/CETP family protein 2.53782 col-136 2.53783 abu-6 Uncharacterized protein 2.53584 fmo-1 Flavin-containing monooxygenase 2.531

85 grl-16 2.51786 C33G3.4 Predicted beta-mannosidase 2.51387 F32B4.2 Translocase of outer mitochondrial membrane complex, subunit TOM20 2.50988 Y52B11B.1 2.498

89 T06E4.12 2.49890 K06H6.1 Uncharacterized protein 2.48291 C26F1.1 2.448

92 col-167 Collagens (type IV and type XIII), and related proteins 2.44

metallocarboxypeptidase activity

Downstream Of DAF-16; RNAi lifespan variant Murphy 2003

GROUND domains (extracellular cysteine-containing domain sometimes associated with HOG domains)

93 nas-36 astacin-like protease 2.43994 abu-10 Uncharacterized protein 2.43995 C23H4.7 2.43896 R03C1.1 2.428

97 grl-21 2.41798 nas-27 Meprin A metalloprotease 2.411

99 K06H6.2 Uncharacterized protein 2.41100 col-168 Collagens (type IV and type XIII), and related proteins 2.406101 pqn-79 Uncharacterized protein 2.406

102 cutl-12 Cuticulin precursor 2.404103 T16G12.1 Puromycin-sensitive aminopeptidase and related aminopeptidases 2.404104 B0403.5 2.393105 R07E3.2 2.388106 grl-27 UDP-glucuronosyl and UDP-glucosyl transferase 2.366107 galt-1 galactosyltransferase 2.357108 pqn-36 Tetraspanin family integral membrane protein 2.343109 nas-8 Meprin A metalloprotease 2.333

110 grd-14 Unnamed protein 2.322111 pqn-54 Uncharacterized protein 2.321112 W09G12.10 2.314113 jud-4 2.312114 npa-1 2.312115 F17B5.8 2.306116 col-145 Collagens (type IV and type XIII), and related proteins 2.3117 K10H10.10 2.3118 C06E1.3 Uncharacterized conserved protein 2.298119 F49F1.5 Secreted surface protein 2.297

120 F55D12.2 2.296121 pqn-91 Uncharacterized protein 2.292122 ncr-2 Cholesterol transport protein (Niemann-Pick C disease protein) 2.291123 lagr-1 Protein transporter of the TRAM (translocating chain-associating membrane) superfamily 2.29124 tts-2 2.288125 gst-38 Glutathione S-transferase 2.288126 ugt-22 UDP-glucuronosyl and UDP-glucosyl transferase 2.286127 col-130 Collagens (type IV and type XIII), and related proteins 2.284

128 F35H10.10 2.283

129 Y52E8A.3 Thioredoxin, nucleoredoxin and related proteins 2.278130 Y47D7A.15 2.272131 C01G6.9 2.269

132 Y71G12B.25 2.266133 K01D12.5 2.266134 grl-4 2.266135 ubc-23 UBiquitin Conjugating enzyme 2.254136 cutl-11 Cuticulin precursor 2.253137 Y43C5B.2 Protein tyrosine kinase 2.252138 pqn-5 Uncharacterized protein 2.251139 nas-22 astacin-like protease 2.245

140 cdf-2 Cation Diffusion Facilitator 2.242141 C10G8.3 Serine proteinase inhibitor (KU family) 2.241142 cut-4 Cuticulin precursor 2.22

GROUND domains (extracellular cysteine-containing domain sometimes associated with HOG domains)

Glutamate-gated metabotropic ion channel receptor subunit GRM2 and related subunits, G-protein coupled receptor superfamily

143 nspb-11 Nematode Specific Peptide family, group B 2.203144 nars-2 Asparagine synthase (glutamine-hydrolyzing) 2.2145 T05C3.6 2.196146 C14C6.6 Extracellular protein with conserved cysteines 2.195147 col-150 Collagens (type IV and type XIII), and related proteins 2.19

148 toh-1 Meprin A metalloprotease 2.183149 M01A12.3 2.179150 B0496.2 Unnamed protein 2.176

151 K02E11.10 2.169152 C10C5.3 Aminoacylase ACY1 and related metalloexopeptidases 2.165153 col-166 Collagens (type IV and type XIII), and related proteins 2.163154 F56A4.4 2.162155 col-58 2.158156 F19B6.3 Unnamed protein 2.151157 dve-1 SATB1 matrix attachment region binding protein 2.151158 pqn-74 Uncharacterized protein 2.15

159 T21C9.9 2.137160 ifd-1 Nuclear envelope protein lamin, intermediate filament superfamily 2.134161 Y77E11A.14 2.133162 F54C1.1 UDP-glucuronosyl and UDP-glucosyl transferase 2.133163 elo-7 Long chain fatty acid elongase 2.122164 ZK6.8 Uncharacterized conserved protein 2.119165 col-156 Collagens (type IV and type XIII), and related proteins 2.118166 T02C1.1 Predicted E3 ubiquitin ligase 2.113167 col-76 Collagens (type IV and type XIII), and related proteins 2.113168 B0222.11 2.11

169 C34E7.4 Unnamed protein 2.109170 F59D12.2 2.1171 col-125 Collagens (type IV and type XIII), and related proteins 2.1172 col-89 Collagens (type IV and type XIII), and related proteins 2.099173 C05D9.3 Integrin beta subunit (N-terminal portion of extracellular region) 2.097174 osm-7 Unnamed protein 2.096175 Y32F6B.1 Organic anion transporter 2.094176 C54D2.1 2.093

177 Y39G8B.10 2.092178 F47B3.1 Protein tyrosine phosphatase 2.091179 F29D10.2 2.087

180 F48G7.8 Secreted surface protein 2.085181 R10F2.6 2.083182 ZK652.8 2.08183 col-152 Collagens (type IV and type XIII), and related proteins 2.076184 nas-29 astacin-like protease 2.076185 C10C5.5 Aminoacylase ACY1 and related metalloexopeptidases 2.072186 wrt-4 Sonic hedgehog and related proteins 2.06187 ZK1010.4 Fibronectin 2.06

188 Y57G11C.42 2.058189 ugt-6 UDP-glucuronosyl and UDP-glucosyl transferase 2.056190 T20B6.3 2.054

191 abu-1 Uncharacterized protein 2.053192 H12D21.9 2.051

protein tyrosine phosphatase activity

193 mup-4 Fibrillins and related proteins containing Ca2+-binding EGF-like domains 2.047194 Y4C6B.2 Amino acid transporters 2.043195 haf-9 Peptide exporter, ABC superfamily 2.041196 C34E7.3 2.038197 lgc-21 2.037

198 nspb-8 2.029199 C31B8.12 Predicted secreted small molecules methylase 2.029200 ugt-4 UDP-glucuronosyl and UDP-glucosyl transferase 2.029

201 ttr-32 Uncharacterized protein with conserved cysteine 2.027202 K09C8.7 2.023203 col-91 Collagens (type IV and type XIII), and related proteins 2.017204 W02B12.13 2.011205 H14N18.4 2.011206 Y38F1A.8 FGF receptor activating protein 1 2.003207 col-174 Collagens (type IV and type XIII), and related proteins 2.001208 H20E11.3 Unnamed protein 2.001

209 gst-13 Glutathione S-transferase 1.998210 C09B8.8 1.997211 ram-5 Cuticulin precursor 1.99212 col-92 Collagens (type IV and type XIII), and related proteins 1.985213 pgp-6 P-glycoprotein subclass of the ATP-binding cassette (ABC) transporter superfamily 1.984214 ltd-1 TGc (transglutaminase/protease-like) domain-containing protein involved in cytokinesis 1.983215 ZC513.1 BPI/LBP/CETP family protein 1.982216 C17B7.12 Unnamed protein 1.981217 inx-17 Innexin-type channels 1.979218 C04A11.1 1.975

219 C11E4.1 1.974220 nlp-33 Unnamed protein 1.974221 H22K11.3 1.974222 C15A11.4 Unnamed protein 1.972223 T25F10.3 Fibrillins and related proteins containing Ca2+-binding EGF-like domains 1.971224 grsp-1 1.968225 col-170 1.967226 F23F1.2 1.966

227 F23D12.1 1.963228 gst-14 Glutathione S-transferase 1.955229 F32A5.2 Peroxidase/oxygenase 1.955

230 T19A5.3 1.953231 F30F8.5 Unnamed protein 1.953232 feh-1 Predicted phosphotyrosine binding protein 1.952233 ugt-5 UDP-glucuronosyl and UDP-glucosyl transferase 1.951234 ZK682.5 Leucine rich repeat 1.947235 R01E6.5 1.947236 K03B8.6 Unnamed protein 1.942237 C15F1.1 Uncharacterized conserved protein 1.942

238 C25B8.8 1.938239 col-118 1.937240 lips-17 Triacylglycerol lipase 1.936

241 F38H4.3 1.932242 bus-19 Predicted membrane protein 1.931

243 T19D2.1 1.926244 gst-10 Glutathione S-transferase 1.922245 col-93 Collagens (type IV and type XIII), and related proteins 1.921246 F28H7.8 Phosphatidylinositol transfer protein SEC14 and related proteins 1.92247 Y71G12B.18 1.919

248 ZK662.2 1.919249 gmd-2 GDP-mannose 4,6 dehydratase 1.918250 pqn-72 1.918

251 ZK829.3 1.915252 F59F3.6 1.912253 dat-1 Sodium-neurotransmitter symporter 1.911254 dct-18 Unnamed protein 1.909

255 F45E1.1 1.907256 haf-4 Peptide exporter, ABC superfamily 1.906257 cyp-34A2 Cytochrome P450 CYP2 subfamily 1.904258 C07A4.2 Defense-related protein containing SCP domain 1.904259 nas-38 Meprin A metalloprotease 1.904

260 phat-2 Secreted surface protein 1.901261 pcp-2 Hydrolytic enzymes of the alpha/beta hydrolase fold 1.899262 dnj-28 dsRNA-activated protein kinase inhibitor P58, contains TPR and DnaJ domains 1.899263 F13B12.3 Unnamed protein 1.898264 B0034.1 1.897265 col-137 1.896266 C36C5.12 Predicted secreted cysteine rich protein found only in C.elegans 1.895267 C42D4.3 Fibronectin 1.895268 C04G6.10 Unnamed protein 1.895269 clec-8 1.894

270 C46H11.2 Flavin-containing monooxygenase 1.893271 C33E10.4 1.889272 F45E1.5 carboxypeptidase A 1.886273 F59B10.3 Unnamed protein 1.882274 C49F8.3 Unnamed protein 1.881275 Y43E12A.2 Predicted Zn-finger protein 1.878276 C42D4.13 1.877277 F53H8.3 Permease of the major facilitator superfamily 1.87

278 grd-15 1.87279 F55E10.6 1.869280 R13H4.8 1.869

281 K02F6.3 WSN domain 1.867282 C06E7.4 1.865283 T04F3.1 1.864284 T01B7.8 Unnamed protein 1.863285 T25E4.1 Unnamed protein 1.862286 K01B6.3 1.862287 T06A4.3 Zinc carboxypeptidase 1.861288 ccch-1 CCCH-type Zn-finger protein 1.859

289 col-161 Collagens (type IV and type XIII), and related proteins 1.855290 col-155 1.853

291 F40G12.9 1.848292 mrp-3 1.847

Metallopeptidase

GROUND domains (extracellular cysteine-containing domain sometimes associated with HOG domains)

GROUND domains (extracellular cysteine-containing domain sometimes associated with HOG domains)

293 dim-1 Immunoglobin and related proteins 1.843294 T16A9.4 M13 family peptidase 1.843295 F33A8.7 1.843296 C27D9.2 1.842297 T02E1.6 1.841

298 nhx-2 Sodium/hydrogen exchanger protein 1.84299 nas-30 Meprin A metalloprotease 1.84300 C14H10.2 1.835

301 col-113 Collagens (type IV and type XIII), and related proteins 1.833302 ZK262.3 Predicted lipase 1.831303 nas-22 astacin-like protease 1.83304 col-49 Collagens (type IV and type XIII), and related proteins 1.829305 H10E21.4 Calmodulin and related proteins (EF-Hand superfamily) 1.825306 F53F1.5 Unnamed protein 1.823307 ZC334.12 1.822308 C18E9.8 1.82

309 ugt-10 1.819

310 grl-1 1.818311 T27A1.5 Amino acid transporters 1.818312 C18E9.7 1.813313 F48B9.2 1.811314 ZK1251.3 Steroid reductase 1.809315 ZK809.1 Protein tyrosine phosphatase 1.808316 prk-2 Serine/threonine protein kinase 1.807317 Y32F6A.4 Amino acid transporters 1.802318 D1086.3 Uncharacterized protein 1.802319 nnt-1 Unnamed protein 1.802

320 Y18H1A.15 1.794321 kin-16 Fibroblast/platelet-derived growth factor receptor and related receptor tyrosine kinases 1.792322 F27C1.3 Uncharacterized protein 1.791323 tag-297 1.789324 C15C7.6 1.789325 C26B9.3 1.788326 inx-18 Innexin-type channels 1.786327 F09B12.3 Uncharacterized conserved protein Lama 1.775

328 F49E12.12 1.773329 F21A3.2 Purple acid phosphatase 1.771330 C01B10.4 Carboxylesterase and related proteins 1.77

331 ptr-3 Predicted membrane protein (patched superfamily) 1.77332 Y82E9BR.21 1.768333 tsp-14 1.768334 C44C10.9 1.765335 C46F11.6 1.765336 col-169 1.763337 T21D12.14 1.761338 ifb-2 Nuclear envelope protein lamin, intermediate filament superfamily 1.761

339 BE10.2 Sterol C5 desaturase 1.761340 F46C5.2 1.759341 col-61 Collagens (type IV and type XIII), and related proteins 1.757

342 C01G6.2 Uncharacterized protein 1.754

GROUND domains (extracellular cysteine-containing domain sometimes associated with HOG domains)

343 F11E6.8 Protein tyrosine kinase 1.752344 F38B6.4 1.752345 col-10 Collagens (type IV and type XIII), and related proteins 1.75346 T25B9.10 Inositol polyphosphate 5-phosphatase and related proteins 1.747347 Y65B4A.2 Cysteine proteinase Cathepsin L 1.746

348 Y39F10C.1 Uncharacterized protein 1.744349 R11A5.7 Zinc carboxypeptidase 1.743350 ugt-51 UDP-glucuronosyl and UDP-glucosyl transferase 1.742

351 F13H6.1 Zn-finger 1.742352 ttll-15 1.742353 fkb-4 FKBP-type peptidyl-prolyl cis-trans isomerase 1.741354 C05D10.4 Unnamed protein 1.741355 acr-8 Acetylcholine receptor 1.74356 Y102A11A.3 1.738357 tag-278 1.738358 hog-1 Sonic hedgehog and related proteins 1.738

359 T11G6.3 Permease of the major facilitator superfamily 1.737360 Y47G6A.19 Zinc carboxypeptidase 1.736361 col-81 Collagens (type IV and type XIII), and related proteins 1.735362 nspb-6 Unnamed protein 1.733363 wht-5 Transporter, ABC superfamily (Breast cancer resistance protein) 1.732364 ptr-24 1.732365 cutl-20 Cuticulin precursor 1.731366 C36C5.15 Predicted secreted cysteine rich protein found only in C.elegans 1.731367 tyr-4 Predicted tyrosinase 1.73368 C09F9.1 Unnamed protein 1.729

369 C04G6.2 1.727370 F01D5.10 Chondroitin 6-sulfotransferase and related sulfotransferases 1.726371 H06H21.8 Predicted small molecule kinase 1.725

372 grl-31 1.725373 dao-4 1.723374 F46C8.8 1.722375 T20D4.15 Predicted secreted cysteine rich protein found only in C.elegans 1.722376 ugt-61 Unnamed protein 1.721377 abu-7 Uncharacterized protein 1.719

378 F41G3.3 1.718379 ZK1010.6 Unnamed protein 1.715380 C38D4.7 1.714

381 F57G8.5 Na+/H+ antiporter 1.714382 apl-1 Beta amyloid precursor protein 1.713383 col-165 Collagens (type IV and type XIII), and related proteins 1.71384 ZK180.6 1.71385 F45E6.1 1.707386 ram-2 Collagens (type IV and type XIII), and related proteins 1.707387 W03G11.2 Cell cycle control protein 1.705388 col-17 Collagens (type IV and type XIII), and related proteins 1.704

389 C48B4.1 Acyl-CoA oxidase 1.703390 T27A3.5 1.703391 1.702

392 F33C8.4 1.7

Glycinamide ribonucleotide synthetase (GARS)/Aminoimidazole ribonucleotide synthetase (AIRS)

GROUND domains (extracellular cysteine-containing domain sometimes associated with HOG domains)

393 ZK287.1 1.698394 D2096.6 Unnamed protein 1.698395 dsc-4 Microsomal triglyceride transfer protein 1.697396 M60.2 Placental protein 11 1.697397 pes-8 1.692

398 cyp-32A1 1.692399 M05B5.1 Protein tyrosine phosphatase 1.691400 Y82E9BR.23 1.689

401 C54F6.3 Chondroitin 6-sulfotransferase and related sulfotransferases 1.687402 spp-23 1.685403 T06E4.10 1.685404 ugt-47 UDP-glucuronosyl and UDP-glucosyl transferase 1.684405 F41B4.1 1.683406 F45E1.4 1.682407 pqn-57 Uncharacterized protein 1.682408 Y45G12C.1 Unnamed protein 1.682

409 R07H5.9 1.677410 K10C2.1 Serine carboxypeptidases (lysosomal cathepsin A) 1.675411 pqn-40 1.675412 pqn-63 1.674413 pbo-4 Sodium/hydrogen exchanger protein 1.674414 C06A1.7 1.673415 clec-209 C-type lectin 1.672416 clec-84 C-type lectin 1.667417 sdz-3 Unnamed protein 1.666418 T17H7.7 1.666

419 C06A1.6 Unnamed protein 1.665420 clec-70 1.665421 Y66A7A.4 Unnamed protein 1.664422 wht-1 Transporter, ABC superfamily (Breast cancer resistance protein) 1.663423 clec-218 1.662424 Y62H9A.12 1.662425 cutl-21 1.66426 R05D7.2 1.659

427 Y18H1A.9 Zinc carboxypeptidase 1.659428 C26B9.5 Hydrolytic enzymes of the alpha/beta hydrolase fold 1.659429 col-97 Collagens (type IV and type XIII), and related proteins 1.657

Please, see next tab for downregulated genes

1500 bp upstream of each of these genes was analyzed for presence of SKN-1 binding sites.

3100

210

10221101

000

00001011

3201

0

0122210

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200

SKN-1 site* TTDTCATC

GATGAHAA * (D=A/G/T) Reverse complement GATGAHAA (H=T/C/A); More restrictive version of the SKN-1 canonical motif: (WWTRTACT, W=A/T, R=A/G, calculated to occur randomly 1/2048bp) is calculated to occur at random 1/10923 bp.

00122

100

00111020

0110010022

01010000

023

00010

0000

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0

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00120100

0100011111

10000220

1

000

10000000

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13010000

2010211110

10100200

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13000000

000

00

10101

001

12143013

1210010000

00111120

002

01000000

201

00

31022

010

0000

00100

1100002010

10010020

010

01011000

00

10

00000

102

00000120

2

0000201100

00100010

101

00001100

000

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002

01010202

0011110001

010

001011

011

11000000

000

0

20010

001

21100000

1100140210

01010101

010

AA (H=T/C/A); More restrictive version of the SKN-1 canonical motif: (WWTRTACT, W=A/T, R=A/G, calculated to occur randomly 1/2048bp) is calculated to occur at random 1/10923 bp.

Supplementary Table S3

SKN-1-dependent downregulated genes under reduced IIS (ranked by SAM score)

SAM Rank KOG (euKaryotic Orthologous Group) Title1 T20D4.7 Thioredoxin, nucleoredoxin and related proteins -5.0622 pes-2.2 F-box domain, increased lifespan by RNAi -4.8163 H04D03.4 similar to human F-box/LRR-repeat protein 14 -4.5394 btb-11 BTB domain protein -4.4465 skr-8 SCF ubiquitin ligase, Skp1 component -3.8486 Y25C1A.6 RNAi results in reduced body size -3.8257 T25E12.6 Uncharacterized protein -3.817

8 cyp-13A5 -3.771

9 F42C5.3 -3.759

10 cyp-13A4 -3.73911 nspe-7 Nematode Specific Peptide family, group E -3.63112 C45H4.14 Unnamed protein -3.62613 skr-10 SCF ubiquitin ligase, Skp1 component -3.616

14 W08A12.4 -3.61615 skr-7 SCF ubiquitin ligase, Skp1 component -3.54516 ZC412.8 Unnamed protein -3.52617 ZK829.9 Permease of the major facilitator superfamily -3.42918 F26G5.1 RNAi embryonic lethal -3.419

19 F15D3.8 -3.40820 T23F6.7 Uncharacterized protein -3.38421 C01G6.3 Uncharacterized protein -3.32722 T24C2.2 RNAi embryonic lethal -3.30123 skr-15 SCF ubiquitin ligase, Skp1 component -3.24224 R04D3.3 Unnamed protein -3.21125 F45C12.15 Homeodomain -3.19826 skr-13 SCF ubiquitin ligase, Skp1 component -3.19727 F08F3.6 F-box domain -3.19628 btb-6 BTB domain protein -3.18729 B0507.10 Unnamed protein -3.16230 E_BE45912.2 Tight junction protein, claudin-like -3.14631 clec-222 RNAi embryonic lethal -3.103

32 gst-24 -3.09633 ztf-25 Zn-finger -3.0834 ech-7 Enoyl-CoA hydratase -3.00235 fbxb-67 Predicted transposase -2.99836 ZK813.7 Uncharacterized protein -2.99437 F14F8.8 Uncharacterized protein -2.99138 fkh-4 Transcription factor of the Forkhead/HNF3 family -2.98839 fbxc-36 F-box domain -2.98140 scl-25 Defense-related protein containing SCP domain -2.97241 Y57G11B.8 -2.96542 Y39B6A.24 Aspartyl protease -2.95843 F53F8.3 Predicted E3 ubiquitin ligase -2.95644 C10G8.4 TIL-domain protease inhibitor -2.95145 clec-91 C-type lectin -2.93546 fbxc-32 F-box domain -2.93147 T22C1.4 -2.92548 scl-24 Defense-related protein containing SCP domain -2.91949 K04G2.10 -2.90250 Y39B6A.10 -2.89251 F13G11.3 -2.8952 cav-1 Caveolin -2.86253 C31B8.4 Uncharacterized protein -2.84754 F47G4.2 ZYG-11-like proteins -2.84455 Y43C5A.3 -2.84

Gene Public Name

Score(d)

lifespan decreased by RNAi, induced by cadmium exposure and RNAi results in decreased cadmium stress resistanceinduced by cadmium exposure and RNAi results in decreased cadmium stress resistance lifespan decreased by RNAi, induced by cadmium exposure and RNAi results in decreased cadmium stress resistance

induced by cadmium exposure and RNAi results in decreased cadmium stress resistance

RNAi knock-down increased oxidative stress resistance and increase lifespan

Glutathione S-transferase, RNAi hypersensitive to oxidative stress

56 B0507.8 Unnamed protein -2.83757 bath-9 Uncharacterized protein, contains BTB/POZ domain -2.83658 fbxa-164 Uncharacterized protein -2.8359 F13E9.14 -2.82960 F31C3.5 -2.82761 C47F8.1 F-box domain -2.79662 T16G12.8 -2.78863 F15A4.10 -2.7864 F12E12.1 -2.77865 F58E1.13 Uncharacterized protein -2.76566 lsy-27 Zn-finger -2.76567 W02D9.7 -2.76568 Y116A8C.22 Chromatin remodeling protein, contains PHD Zn-finger -2.76269 T26F2.3 -2.75570 ZC308.4 -2.75571 C36C9.1 Unnamed protein -2.74872 fbxc-42 F-box domain -2.72973 Y47H9C.1 Uncharacterized protein -2.72374 gyg-2 Glycosyl transferase, family 8 - glycogenin -2.72175 fkh-3 Transcription factor of the Forkhead/HNF3 family -2.7276 F22E5.17 -2.71777 T02G6.5 F-box domain -2.70278 nas-3 Meprin A metalloprotease -2.69379 W04E12.2 Unnamed protein -2.69280 R04D3.2 Unnamed protein -2.69

81 H04M03.3 -2.68482 R04D3.4 -2.68383 F14D7.2 Nucleolar GTPase/ATPase p130 -2.67684 K07H8.11 -2.66385 Y22D7AR.10 Histone acetyltransferase (MYST family) -2.65286 Y66D12A.7 Mitochondrial DNA polymerase accessory subunit -2.64887 clec-87 C-type lectin -2.64688 Y6E2A.5 -2.64689 F14B6.3 Unnamed protein -2.64290 F23D12.10 -2.64291 F56D5.5 Tropomysin domain -2.63592 F14H3.3 Unnamed protein -2.63393 K10C2.7 -2.63

94 sepa-1 -2.61695 F14H3.4 -2.61596 C54F6.5 -2.6197 skr-12 SCF ubiquitin ligase, Skp1 component -2.60698 W03F11.1 chitin-binding peritrophin-A domain -2.60299 C06E2.5 -2.602100 rgs-11 G protein signaling regulators -2.598101 EEED8.13 -2.597102 fbxc-33 F-box domain -2.592103 C50D2.6 Unnamed protein -2.581104 T04D3.1 Uncharacterized coiled-coil containing protein -2.58105 T27A1.2 Uncharacterized protein -2.58106 dut-1 dUTPase -2.571107 F54H12.5 -2.568108 F19H6.4 Steroid reductase -2.566109 rgs-9 G protein signaling regulators -2.564110 K01G12.3 -2.556111 ZK813.2 -2.547112 ttr-42 -2.547113 lbp-8 -2.535114 F44G3.10 Unnamed protein -2.534115 K08F9.3 -2.525116 EEED8.15 -2.517117 meg-1 Unnamed protein -2.514118 Y48E1B.8 Uncharacterized protein -2.505119 F14F9.6 -2.501120 Y41D4B.17 Unnamed protein -2.499121 cnc-2 Unnamed protein -2.498122 gln-6 Glutamine synthetase -2.496123 Y71A12B.12 -2.495124 Y37D8A.19 Unnamed protein -2.494125 C35E7.1 Uncharacterized coiled-coil containing protein -2.493

Dehydrogenases with different specificities (related to short-chain alcohol dehydrogenases)

CREB binding protein/P300 and related TAZ Zn-finger proteins

126 C50E3.13 Unnamed protein -2.483127 F57C2.4 -2.482128 ttr-26 Uncharacterized protein with conserved cysteine -2.475129 F21C10.4 Uncharacterized protein, contains CX module -2.474130 T01C3.3 Predicted E3 ubiquitin ligase -2.474131 C17E7.12 -2.474132 F23D12.2 -2.472133 ceh-49 CCAAT displacement protein and related homeoproteins -2.471134 F27D4.8 -2.468135 F41G3.10 -2.467136 F18A1.7 Unnamed protein -2.464137 dsl-2 Proteins containing Ca2+-binding EGF-like domains -2.46138 sea-1 TBX2 and related T-box transcription factors -2.456139 ZC373.2 Unnamed protein -2.446140 F08F1.4 -2.435141 W02F12.3 -2.422142 T05H4.15 Unnamed protein -2.418143 C55B6.1 -2.416144 T04D3.5 -2.415145 H29C22.1 -2.413146 F54D10.7 -2.4147 K09E3.7 Unnamed protein -2.396148 C14B1.2 -2.396149 sip-1 Alpha crystallins -2.387150 C04A11.2 -2.387151 Y46G5A.8 Unnamed protein -2.385152 C50E3.11 -2.383153 K09H9.5 -2.382154 T02G5.11 Unnamed protein -2.376155 cpr-4 Cysteine proteinase Cathepsin L -2.368156 ZK177.1 -2.363157 nhr-147 Nuclear hormone receptor -2.362158 F46F2.3 -2.361159 pos-1 CCCH-type Zn-finger protein -2.357160 fbxc-50 F-box domain -2.357161 B0416.4 Predicted E3 ubiquitin ligase -2.355162 W06D11.1 -2.352163 clec-223 -2.35164 F48C1.8 -2.345165 ZK813.1 -2.345

166 dad-1 -2.344167 ZK1053.4 Uncharacterized protein -2.342168 F32D1.6 -2.341169 Y34F4.2 -2.338170 B0348.2 Unnamed protein -2.336171 gln-5 Glutamine synthetase -2.329172 C04H5.7 -2.326173 F26H9.4 Nicotinamide mononucleotide adenylyl transferase -2.324174 Y23H5A.2 -2.323175 F55B11.3 Unnamed protein -2.322176 C17E7.4 Unnamed protein -2.316177 dsl-3 Proteins containing Ca2+-binding EGF-like domains -2.31178 F33E2.5 C-type lectin -2.31179 K11D12.13 -2.307180 ttr-50 Uncharacterized protein with conserved cysteine -2.306181 Y65B4BR.8 Uncharacterized conserved protein -2.277182 abf-5 Unnamed protein -2.274183 DY3.8 -2.271184 spp-20 -2.267185 F02D10.6 Unnamed protein -2.263186 Y49F6C.8 -2.258187 F35B12.3 -2.251188 Y52E8A.2 Predicted E3 ubiquitin ligase -2.247189 F37B4.10 -2.247190 hlh-2 -2.241191 C05D9.7 -2.24192 mom-2 Wnt family of developmental regulators -2.239193 T12G3.6 -2.235194 Y58A7A.4 Unnamed protein -2.232195 cdc-25.3 Uncharacterized conserved protein -2.218196 D1054.11 -2.213

Defender against cell death protein/oligosaccharyltransferase, epsilon subunit

197 C05C10.5 -2.208198 E04F6.8 Unnamed protein -2.205199 F14D7.7 Uncharacterized protein -2.203200 ZK632.10 Uncharacterized conserved protein -2.202201 Y52B11A.8 Unnamed protein -2.201202 F40G12.11 -2.195203 W02D9.6 -2.191204 Y37D8A.4 -2.189205 Y62H9A.5 Unnamed protein -2.184206 F42G2.6 Unnamed protein -2.183207 C28C12.4 Predicted alpha-helical protein -2.181208 Y46G5A.20 -2.176209 crn-4 Predicted exonuclease -2.174210 T26H5.10 -2.164211 C52A10.3 Uncharacterized protein -2.161212 F44E7.5 -2.156213 C27B7.9 -2.156214 clec-88 -2.155215 C10B5.1 -2.151216 C49F5.3 Unnamed protein -2.149217 lsd-1 Amine oxidase -2.149218 F22G12.1 -2.141

219 F57B9.3 -2.137220 K11H12.11 -2.133221 F12E12.3 Unnamed protein -2.125222 T13B5.9 -2.123223 nos-2 Uncharacterized coiled-coil containing protein -2.119224 C25F9.11 -2.119225 ins-34 -2.112

226 ZK105.1 -2.109227 F17A2.13 -2.102228 F27C8.6 -2.098229 apc-16 -2.095230 F22D6.14 -2.086231 btb-7 BTB domain protein -2.083232 ztf-11 Transcription factor containing C2HC type Zn finger -2.077233 F59A6.12 -2.075234 C44C1.6 -2.073235 Y37D8A.25 -2.065236 T27A8.2 -2.062237 Y41D4B.18 -2.057238 gei-12 Unnamed protein -2.052239 ZK154.5 Unnamed protein -2.052240 ttr-21 Uncharacterized protein with conserved cysteine -2.049241 cpg-1 Unnamed protein -2.046242 inx-3 Innexin-type channels -2.043243 Y62H9A.6 Unnamed protein -2.042244 pzf-1 -2.04245 Y54G2A.48 -2.04246 math-10 Uncharacterized protein, contains BTB/POZ domain -2.037247 E02H1.5 Carnitine deficiency associated protein -2.034248 C48B4.7 Unnamed protein -2.034249 aps-3 -2.027250 vang-1 Signaling protein van gogh/strabismus -2.027251 clec-210 C-type lectin -2.025252 T04D3.8 -2.023253 C23G10.11 -2.022254 T07D4.5 -2.022

255 B0281.5 -2.017256 Y106G6H.6 -2.015257 nspc-13 Unnamed protein -2.008258 ZC196.4 -2.007259 C37C3.9 Uncharacterized protein, contains BTB/POZ domain -2.004260 inx-2 Innexin-type channels -2.004261 F52C6.3 Ubiquitin and ubiquitin-like proteins -1.99262 B0238.12 Uncharacterized protein -1.987263 ref-1 Unnamed protein -1.987264 C39B5.2 -1.98265 K08E4.2 Uncharacterized conserved protein -1.977

Translation initiation factor 4F, helicase subunit (eIF-4A) and related helicases

Predicted secreted cysteine rich protein found only in C.elegans

Polymerase delta-interacting protein PDIP1 and related proteins, contain BTB/POZ domain

266 dhs-26 -1.976267 D1054.10 -1.971

268 ZK105.5 -1.97269 pqn-60 Predicted alpha-helical protein -1.969270 gna-2 Glucosamine-phosphate N-acetyltransferase -1.963271 far-3 -1.961272 cyp-13A10 Cytochrome P450 CYP3/CYP5/CYP6/CYP9 subfamilies -1.961273 T19H5.7 -1.953274 C46E10.9 Zn-finger -1.952275 cnc-7 Unnamed protein -1.952276 Y51H7C.3 -1.95277 T06D4.1 -1.947278 C53B7.2 -1.945

279 taf-9 -1.943280 R05H5.3 Thioredoxin, nucleoredoxin and related proteins -1.938281 Y69A2AR.25 Unnamed protein -1.936

282 Y50D4B.6 -1.934283 B0432.10 -1.929284 fbxa-170 Uncharacterized protein -1.928285 B0511.7 Nuclear inhibitor of phosphatase-1 -1.927286 W08A12.2 -1.922287 F25H9.6 -1.921288 fbxb-59 Predicted transposase -1.912289 C30H6.12 -1.91290 cyp-33D3 Cytochrome P450 CYP2 subfamily -1.909291 F08G2.5 -1.908292 pho-14 Lysosomal & prostatic acid phosphatases -1.905293 ceh-40 -1.902294 ekl-5 -1.896295 Y39A1A.12 -1.895296 C41H7.9 -1.894297 rpb-11 RNA polymerase, subunit L -1.893298 ZK688.7 -1.893299 T19B10.6 Uncharacterized conserved protein -1.892300 E04D5.4 -1.892301 T22C8.4 -1.892302 F54D10.5 -1.891303 Y110A2AL.1 Unnamed protein -1.891304 ssup-72 -1.891305 M116.2 -1.891306 cdr-5 -1.89307 skr-17 SCF ubiquitin ligase, Skp1 component -1.885308 F46B6.4 Predicted GTP binding protein -1.881309 clec-97 C-type lectin -1.878310 clec-61 Lectin C-type domain/CUB domain -1.871

311 puf-6 -1.871312 F54D5.11 Transcription initiation factor IIE, beta subunit -1.869313 F14H3.6 -1.868

314 hpr-17 -1.867315 Y66D12A.6 -1.866316 fbxc-28 F-box domain -1.861317 F02H6.3 Unnamed protein -1.858318 Y75B8A.18 -1.858319 C41H7.3 Uncharacterized protein -1.858320 acs-19 -1.856321 Y41D4B.16 Unnamed protein -1.854322 clec-147 C-type lectin -1.853323 cpg-2 Unnamed protein -1.851324 F54C4.4 -1.848325 C09B8.5 -1.848326 W03F9.9 Reductases with broad range of substrate specificities -1.845327 nhr-20 Hormone receptors -1.843328 C06E4.8 -1.838329 Y48B6A.16 -1.837330 skr-5 SCF ubiquitin ligase, Skp1 component -1.835331 cyp-13B2 Cytochrome P450 CYP3/CYP5/CYP6/CYP9 subfamilies -1.833332 Y37H2A.14 -1.832

Predicted secreted cysteine rich protein found only in C.elegans

Transcription initiation factor TFIID, subunit TAF9 (also component of histone acetyltransferase SAGA)

Fibroblast/platelet-derived growth factor receptor and related receptor tyrosine kinases

domain)

proteins

proteins

Translational repressor Pumilio/PUF3 and related RNA-binding proteins (Puf superfamily)

Checkpoint RAD17-RFC complex, RAD17/RAD24 component

333 lir-1 -1.829334 B0304.2 -1.826335 Y37E11B.3 Uncharacterized conserved protein -1.826336 Y57G11B.5 Unnamed protein -1.824337 bath-28 -1.822338 ZC168.3 -1.815339 T19C9.8 -1.814340 C17E7.9 Unnamed protein -1.812341 fbxa-83 Uncharacterized protein -1.807342 F52B5.7 -1.803343 ZK688.9 -1.8344 D1054.14 Predicted PRP38-like splicing factor -1.799345 btb-17 -1.799346 CD4.7 -1.797347 F08D12.3 -1.796348 R09A8.2 Unnamed protein -1.794349 bed-2 -1.794350 B0454.9 Uncharacterized protein -1.792351 K11D12.12 -1.787

352 egg-2 -1.785353 lys-4 N-acetylmuraminidase/lysozyme -1.782354 Y39A1A.13 -1.781355 C35E7.5 Uncharacterized protein -1.776356 T28C6.3 Unnamed protein -1.776357 nhr-231 -1.775358 oma-2 Unnamed protein -1.773359 rgs-10 G protein signaling regulators -1.769360 Y49A3A.1 -1.769361 fbxa-132 -1.768362 R09F10.8 -1.765363 F58A4.6 -1.763364 ZK616.3 Trypsin -1.758365 taf-11.2 Transcription initiation factor TFIID, subunit TAF11 -1.756366 lys-7 N-acetylmuraminidase/lysozyme -1.754367 C08F11.12 Unnamed protein -1.753

368 rme-2 -1.749369 try-1 -1.749370 nfya-1 CCAAT-binding factor, subunit B (HAP2) -1.749371 fat-5 Fatty acid desaturase -1.748372 trt-1 -1.747373 Y54G9A.5 -1.747374 mtm-9 -1.746375 C45G9.2 tRNA-dihydrouridine synthase -1.745376 C08A9.8 Uncharacterized protein -1.744377 ced-8 Uncharacterized conserved protein -1.744378 fbxa-215 Uncharacterized protein -1.743379 nasp-2 Cell cycle-regulated histone H1-binding protein -1.74380 dyrb-1 Dynein-associated protein Roadblock -1.74381 spp-18 -1.739382 fipr-2 -1.738383 W06D11.3 -1.737

384 R06F6.6 -1.736385 Y43F8B.9 -1.733386 F32D1.7 -1.732387 F11C3.1 -1.731388 K11B4.2 Uncharacterized conserved protein -1.729389 nhr-2 -1.728390 C33C12.9 -1.726391 EEED8.3 -1.724392 F31E9.6 Uncharacterized conserved protein -1.722393 W01D2.5 -1.722394 F46F2.5 -1.722

395 B0564.3 -1.721396 Y45F10C.2 Unnamed protein -1.721397 rgs-8.2 G protein signaling regulators -1.72398 F43D2.1 -1.719399 Y22D7AL.9 -1.718400 C41D11.9 Predicted GTP-binding protein -1.718

Low-density lipoprotein receptors containing Ca2+-binding EGF-like domains

Low-density lipoprotein receptors containing Ca2+-binding EGF-like domains

TERT

Transcription factor zerknullt and related HOX domain proteins

family

Bestrophin (Best vitelliform macular dystrophy-associated protein)

401 F59A7.2 Unnamed protein -1.718402 M01B2.13 -1.713403 Y39B6A.37 -1.711404 F09E10.1 -1.71405 rmd-1 Uncharacterized conserved protein -1.709406 T07C4.12 -1.709407 srd-14 -1.709408 C50E3.12 Unnamed protein -1.709409 F19C7.3 -1.706410 F33E2.4 -1.705411 pch-2 AAA+-type ATPase -1.705412 C06H2.7 -1.702413 K07A1.6 Uncharacterized protein -1.702414 R05G9.3 -1.702

415 tag-52 -1.701416 F53A9.8 -1.7417 C16C8.11 Ubiquitin and ubiquitin-like proteins -1.696418 hmp-2 Armadillo/beta-Catenin/plakoglobin -1.691419 F28A10.5 Uncharacterized protein -1.69420 F14H3.5 -1.69421 B0035.18 -1.69422 F47B8.1 Uncharacterized protein -1.689423 sqv-4 UDP-glucose/GDP-mannose dehydrogenase -1.686424 oma-1 CCCH-type Zn-finger protein -1.685425 Y54G2A.47 -1.684426 sir-2.3 Sirtuin 4 and related class II sirtuins (SIR2 family) -1.683427 ztf-9 -1.682428 R12G8.1 Serine/threonine protein kinase -1.682429 frg-1 Predicted actin-bundling protein -1.681430 E02H9.7 -1.681431 C01G10.7 Citrate lyase, beta subunit -1.68432 thn-2 -1.68433 W05H9.4 -1.679434 clec-146 -1.679435 tag-115 -1.678436 cnc-3 Unnamed protein -1.677437 fbxa-36 -1.675438 Y39B6A.13 -1.673439 pqn-88 -1.673440 lin-37 -1.672441 F09C8.1 -1.672442 cyb-3 -1.668443 mesp-1 -1.666444 pri-2 Eukaryotic-type DNA primase, large subunit -1.663445 C49F5.6 Uncharacterized protein -1.663446 K09H9.2 Uncharacterized conserved protein -1.662447 fbxa-135 -1.661448 C24D10.5 Unnamed protein -1.66449 skpt-1 -1.66450 clec-12 C-type lectin -1.659451 D1007.8 -1.659452 mxl-1 Upstream transcription factor 2/L-myc-2 protein -1.659453 fbxa-153 Uncharacterized protein -1.656454 F08G12.2 -1.656455 B0513.4 -1.654456 F02H6.2 -1.653457 C08A9.10 -1.652458 Y47G6A.14 Unnamed protein -1.649459 pcn-1 -1.649460 Y43F4B.10 Cyclin-dependent kinase 2-associated protein -1.648461 fipr-13 -1.646462 C56A3.4 -1.643463 F52C12.1 Tyrosyl-DNA phosphodiesterase -1.642464 skr-14 SCF ubiquitin ligase, Skp1 component -1.64465 lin-52 Stress responsive protein -1.64466 F32E10.5 Unnamed protein -1.64467 F38A5.7 Unnamed protein -1.638

468 C17F4.8 -1.638469 C26F1.3 -1.636470 sedl-1 TRAPP 20 K subunit -1.636

Predicted Rho/Rac guanine nucleotide exchange factor/faciogenital dysplasia protein 3

proteins

subunit

proteins

Polymerase delta-interacting protein PDIP1 and related proteins, contain BTB/POZ domain

471 C36B1.14 -1.635

472 srv-7 -1.634473 Y116A8B.1 Unnamed protein -1.634474 H02I12.5 Unnamed protein -1.634475 kbp-4 -1.633476 apc-11 Anaphase-promoting complex (APC), subunit 11 -1.633477 Y41D4B.15 -1.633

Uncharacterized protein with weak similarity to 7-transmembrane receptor