30. Rottiers V, Antebi A (2006) Control of Caenorhabditis elegans life history by nuclear receptor signal transduction. Exp Gerontol 41: 904–909. 31. Edgar R, Domrachev M, Lash AE (2002) Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res 30: 207–210. 32. Zhong M, Niu W, Lu ZJ, Sarov M, Murray JI, et al. (2010) Genome-wide identification of binding sites defines distinct functions for Caenorhabditis elegans PHA-4/FOXA in development and environmental response. PLoS Genet 6: e1000848. doi:10.1371/journal.pgen.1000848. 33. Shostak Y, Van Gilst MR, Antebi A, Yamamoto KR (2004) Identification of C. elegans DAF-12-binding sites, response elements, and target genes. Genes Dev 18: 2529–2544. 34. Chatterjee S, Grosshans H (2009) Active turnover modulates mature microRNA activity in Caenorhabditis elegans. Nature 461: 546–549. 35. Hammell CM, Lubin I, Boag PR, Blackwell TK, Ambros V (2009) nhl-2 Modulates microRNA activity in Caenorhabditis elegans. Cell 136: 926–938. 36. Huang da W, Sherman BT, Lempicki RA (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4: 44–57. 37. Ao W, Gaudet J, Kent WJ, Muttumu S, Mango SE (2004) Environmentally induced foregut remodeling by PHA-4/FoxA and DAF-12/NHR. Science 305: 1743–1746. 38. Bailey TL, Williams N, Misleh C, Li WW (2006) MEME: discovering and analyzing DNA and protein sequence motifs. Nucleic Acids Res 34: W369–373. 39. Musgrove EA, Sutherland RL (2009) Biological determinants of endocrine resistance in breast cancer. Nat Rev Cancer 9: 631–643. 40. Masuyama H, Brownfield CM, St-Arnaud R, MacDonald PN (1997) Evidence for ligand-dependent intramolecular folding of the AF-2 domain in vitamin D receptor-activated transcription and coactivator interaction. Mol Endocrinol 11: 1507–1517. 41. Nasrin N, Ogg S, Cahill CM, Biggs W, Nui S, et al. (2000) DAF-16 recruits the CREB-binding protein coactivator complex to the insulin-like growth factor binding protein 1 promoter in HepG2 cells. Proc Natl Acad Sci U S A 97: 10412–10417. 42. Paradis S, Ailion M, Toker A, Thomas JH, Ruvkun G (1999) A PDK1 homolog is necessary and sufficient to transduce AGE-1 PI3 kinase signals that regulate diapause in Caenorhabditis elegans. Genes Dev 13: 1438–1452. 43. Moss EG (2007) Heterochronic genes and the nature of developmental time. Curr Biol 17: R425–434. 44. Slack FJ, Basson M, Liu Z, Ambros V, Horvitz HR, et al. (2000) The lin-41 RBCC gene acts in the C. elegans heterochronic pathway between the let-7 regulatory RNA and the LIN-29 transcription factor. Mol Cell 5: 659–669. 45. Moss EG, Lee RC, Ambros V (1997) The cold shock domain protein LIN-28 controls developmental timing in C. elegans and is regulated by the lin-4 RNA. Cell 88: 637–646. 46. Banerjee D, Kwok A, Lin SY, Slack FJ (2005) Developmental timing in C. elegans is regulated by kin-20 and tim-1, homologs of core circadian clock genes. Dev Cell 8: 287–295. 47. Jeon M, Gardner HF, Miller EA, Deshler J, Rougvie AE (1999) Similarity of the C. elegans developmental timing protein LIN-42 to circadian rhythm proteins. Science 286: 1141–1146. 48. Coller J, Parker R (2005) General translational repression by activators of mRNA decapping. Cell 122: 875–886. 49. Geiss GK, Bumgarner RE, Birditt B, Dahl T, Dowidar N, et al. (2008) Direct multiplexed measurement of gene expression with color-coded probe pairs. Nat Biotechnol 26: 317–325. 50. Rutherford SL, Lindquist S (1998) Hsp90 as a capacitor for morphological evolution. Nature 396: 336–342. Identification of DAF-12 Target Genes by ChIP-chip 51. Simmer F, Tijsterman M, Parrish S, Koushika SP, Nonet ML, et al. (2002) Loss of the putative RNA-directed RNA polymerase RRF-3 makes C. elegans hypersensitive to RNAi. Curr Biol 12: 1317–1319. 52. Rougvie AE (2001) Control of developmental timing in animals. Nat Rev Genet 2: 690–701. 53. Lambie EJ (2002) Cell proliferation and growth in C. elegans. Bioessays 24: 38–53. 54. Tennessen JM, Opperman KJ, Rougvie AE (2010) The C. elegans develop- mental timing protein LIN-42 regulates diapause in response to environmental cues. Development. 55. Morita K, Han M (2006) Multiple mechanisms are involved in regulating the expression of the developmental timing regulator lin-28 in Caenorhabditis elegans. EMBO J 25: 5794–5804. 56. Grishok A, Pasquinelli AE, Conte D, Li N, Parrish S, et al. (2001) Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing. Cell 106: 23–34. 57. Viswanathan SR, Daley GQ, Gregory RI (2008) Selective blockade of microRNA processing by Lin28. Science 320: 97–100. 58. Waddington CH (1959) Canalization of development and genetic assimilation of acquired characters. Nature 183: 1654–1655. 59. Wang Z, Zhou XE, Motola DL, Gao X, Suino-Powell K, et al. (2009) Identification of the nuclear receptor DAF-12 as a therapeutic target in parasitic nematodes. Proc Natl Acad Sci U S A 106: 9138–9143. 60. Bento G, Ogawa A, Sommer RJ (2010) Co-option of the hormone-signalling module dafachronic acid-DAF-12 in nematode evolution. Nature 466: 494–497. 61. Lehner B, Crombie C, Tischler J, Fortunato A, Fraser AG (2006) Systematic mapping of genetic interactions in Caenorhabditis elegans identifies common modifiers of diverse signaling pathways. Nat Genet 38: 896–903. 62. Karp X, Ambros V (2011) The Developmental Timing Regulator hbl-1 Modulates the Dauer Formation Decision in Caenorhabditis elegans. Genetics 187: 345–353. 63. Puig O, Caspary F, Rigaut G, Rutz B, Bouveret E, et al. (2001) The tandem affinity purification (TAP) method: a general procedure of protein complex purification. Methods 24: 218–229. 64. Hochbaum D, Ferguson AA, Fisher AL (2010) Generation of transgenic C. elegans by biolistic transformation. J Vis Exp. 65. Gengyo-Ando K, Mitani S (2000) Characterization of mutations induced by ethyl methanesulfonate, UV, and trimethylpsoralen in the nematode Caenor- habditis elegans. Biochem Biophys Res Commun 269: 64–69. 66. Soutoglou E, Talianidis I (2002) Coordination of PIC assembly and chromatin remodeling during differentiation-induced gene activation. Science 295: 1901–1904. 67. Johnson WE, Li W, Meyer CA, Gottardo R, Carroll JS, et al. (2006) Model- based analysis of tiling-arrays for ChIP-chip. Proc Natl Acad Sci U S A 103: 12457–12462. 68. Ferguson AA, Springer MG, Fisher AL (2010) skn-1-Dependent and - independent regulation of aip-1 expression following metabolic stress in Caenorhabditis elegans. Mol Cell Biol 30: 2651–2667. 69. Ferguson AA, Fisher AL (2009) Retrofitting ampicillin resistant vectors by recombination for use in generating C. elegans transgenic animals by bombardment. Plasmid 62: 140–145. 70. Martin R, Da¨britz F, Entchev EV, Kurzchalia TV, Kno¨lker H-J (2008) Stereoselective synthesis of the hormonally active (25S)-delta7-dafachronic acid, (25S)-delta4-dafachronic acid, (25S)-dafachronic acid, and (25S)-cholestenoic acid. Org Biomol Chem 6: 4293–4295. 71. Martin R, Schmidt AW, Theumer G, Krause T, Entchev EV, et al. (2009) Synthesis and biological activity of the (25R)-cholesten-26-oic acids–ligands for the hormonal receptor DAF-12 in Caenorhabditis elegans. Org Biomol Chem 7: 909–920. PLoS Genetics | www.plosgenetics.org 16 July 2011 | Volume 7 | Issue 7 | e1002179