Synergistic action of the transcription factors Krüppel homolog 1 and Hairy in juvenile hormone/Methoprene-tolerant-mediated gene-repression in the mosquito Aedes aegypti

English version

Autoři: Tusar T. Saha ^aff001; Sourav Roy ^aff001; Gaofeng Pei ^aff004; Wei Dou ^aff001; Zhen Zou ^aff004; Alexander S. Raikhel ^aff001
Působiště autorů: Department of Entomology and Institute of Integrative Biology, University of California, Riverside, California, United States of America ^aff001; Department of Biological Sciences, Birla Institute of Technology and Science Pilani, K. K. Birla Goa Campus, Goa, India ^aff002; Department of Biological Sciences, University of Texas El Paso, Texas ^aff003; State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, China ^aff004; University of Chinese Academy of Sciences, Beijing, China ^aff005; College of Plant Protection, Southwest University, Chongqing, China ^aff006
Vyšlo v časopise: Synergistic action of the transcription factors Krüppel homolog 1 and Hairy in juvenile hormone/Methoprene-tolerant-mediated gene-repression in the mosquito Aedes aegypti. PLoS Genet 15(10): e32767. doi:10.1371/journal.pgen.1008443
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1008443

Souhrn

Arthropod-specific juvenile hormones control numerous essential functions in development and reproduction. In the dengue-fever mosquito Aedes aegypti, in addition to its role in immature stages, juvenile hormone III (JH) governs post-eclosion (PE) development in adult females, a phase required for competence acquisition for blood feeding and subsequent egg maturation. During PE, JH through its receptor Methoprene-tolerant (Met) regulate the expression of many genes, causing either activation or repression. Met-mediated gene repression is indirect, requiring involvement of intermediate repressors. Hairy, which functions downstream of Met in the JH gene-repression hierarchy, is one such factor. Krüppel-homolog 1, a zinc-finger transcriptional factor, is directly regulated by Met and has been implicated in both activation and repression of JH-regulated genes. However, the interaction between Hairy and Kr-h1 in the JH-repression hierarchy is not well understood. Our RNAseq-based transcriptomic analysis of the Kr-h1-depleted mosquito fat body revealed that 92% of Kr-h1 repressed genes are also repressed by Met, supporting the existence of a hierarchy between Met and Kr-h1 as previously demonstrated in various insects. Notably, 130 genes are co-repressed by both Kr-h1 and Hairy, indicating regulatory complexity of the JH-mediated PE gene repression. A mosquito Kr-h1 binding site in genes co-regulated by this factor and Hairy was identified computationally. Moreover, this was validated using electrophoretic mobility shift assays. A complete phenocopy of the effect of Met RNAi depletion on target genes could only be observed after Kr-h1 and Hairy double RNAi knockdown, suggesting a synergistic action between these two factors in target gene repression. This was confirmed using a cell-culture-based luciferase reporter assay. Taken together, our results indicate that Hairy and Kr-h1 not only function as intermediate downstream factors, but also act together in a synergistic fashion in the JH/Met gene repression hierarchy.

Klíčová slova:

Gene expression – Gene regulation – Hair – Sequence motif analysis – RNA interference – Fats – Luciferase – Mosquitoes

Zdroje

1. Jindra M, Palli SR, Riddiford LM (2013) The juvenile hormone signaling pathway in insect development. Annu Rev Entomol 58: 181–204. doi: 10.1146/annurev-ento-120811-153700 22994547

2. Jindra M, Bellés X, Shinoda T (2015) Molecular basis of juvenile hormone signaling. Curr Opin Insect Sci 11: 39–46. doi: 10.1016/j.cois.2015.08.004 28285758

3. Wilson TG, Fabian J (1986) A Drosophila melanogaster mutant resistant to a chemical analog of juvenile hormone. Dev Biol 118: 190–201. doi: 10.1016/0012-1606(86)90087-4 3095161

4. Ashok M, Turner C, Wilson TG (1998) Insect juvenile hormone resistance gene homology with the bHLH-PAS family of transcriptional regulators. Proc Natl Acad Sci USA 95: 2761–2766. doi: 10.1073/pnas.95.6.2761 9501163

5. Miura K, Oda M, Makita S, Chinzei Y (2005) Characterization of the Drosophila Methoprene -tolerant gene product. Juvenile hormone binding and ligand-dependent gene regulation. FEBS J 272: 1169–1178. doi: 10.1111/j.1742-4658.2005.04552.x 15720391

6. Konopova B, Jindra M (2007) Juvenile hormone resistance gene Methoprene-tolerant controls entry into metamorphosis in the beetle Tribolium castaneum. Proc Natl Acad Sci USA 104: 10488–10493. doi: 10.1073/pnas.0703719104 17537916

7. Charles JP, Iwema T, Epa VC, Takaki K, Rynes J, et al. (2011) Ligand-binding properties of a juvenile hormone receptor, Methoprene-tolerant. Proc Natl Acad Sci USA 108: 21128–21133. doi: 10.1073/pnas.1116123109 22167806

8. Jindra M, Uhlirova M, Charles JP, Smykal V, Hill RJ (2015) Genetic Evidence for Function of the bHLH-PAS Protein Gce/Met As a Juvenile Hormone Receptor. PLoS Genet 11: e1005394. doi: 10.1371/journal.pgen.1005394 26161662

9. Li M, Mead EA, Zhu J (2011) Heterodimer of two bHLH-PAS proteins mediates juvenile hormone-induced gene expression. Proc Natl Acad Sci USA 108: 638–643. doi: 10.1073/pnas.1013914108 21187375

10. Zhang Z, Xu J, Sheng Z, Sui Y, Palli SR (2011) Steroid receptor co-activator is required for juvenile hormone signal transduction through a bHLH-PAS transcription factor, methoprene tolerant. J Biol Chem 286: 8437–8447. doi: 10.1074/jbc.M110.191684 21190938

11. Li M, Liu P, Wiley JD, Ojani R, Bevan DR, et al. (2014) A steroid receptor coactivator acts as the DNA-binding partner of the methoprene-tolerant protein in regulating juvenile hormone response genes. Mol Cell Endocrinol 394: 47–58. doi: 10.1016/j.mce.2014.06.021 25004255

12. Kayukawa T, Minakuchi C, Namiki T, Togawa T, Yoshiyama M, et al. (2012) Transcriptional regulation of juvenile hormone-mediated induction of Krüppel homolog 1, a repressor of insect metamorphosis. Proc Natl Acad Sci USA 109: 11729–11734. doi: 10.1073/pnas.1204951109 22753472

13. Shin SW, Zou Z, Saha TT, Raikhel AS (2012) bHLH-PAS heterodimer of methoprene-tolerant and Cycle mediates circadian expression of juvenile hormone-induced mosquito genes. Proc Natl Acad Sci USA 109: 16576–16581. doi: 10.1073/pnas.1214209109 23012454

14. Kayukawa T, Tateishi K, Shinoda T (2013) Establishment of a versatile cell line for juvenile hormone signaling analysis in Tribolium castaneum. Sci Rep 3: 1570. doi: 10.1038/srep01570 23535851

15. Zou Z, Saha TT, Roy S, Shin SW, Backman TW, et al. (2013) Juvenile hormone and its receptor, methoprene-tolerant, control the dynamics of mosquito gene expression. Proc Natl Acad Sci USA 110: E2173–2181. doi: 10.1073/pnas.1305293110 23633570

16. Cui Y, Sui Y, Xu J, Zhu F, Palli SR (2014) Juvenile hormone regulates Aedes aegypti Kruppel homolog 1 through a conserved E box motif. Insect Biochem Mol Biol 52: 23–32. doi: 10.1016/j.ibmb.2014.05.009 24931431

17. Wang JL, Saha TT, Zhang Y, Zhang C, Raikhel AS (2017) Juvenile hormone and its receptor methoprene-tolerant promote ribosomal biogenesis and vitellogenesis in the Aedes aegypti mosquito. J Biol Chem 292: 10306–10315. doi: 10.1074/jbc.M116.761387 28446607

18. He Q, Wen D, Jia Q, Cui C, Wang J, et al. (2014) Heat shock protein 83 (Hsp83) facilitates methoprene-tolerant (Met) nuclear import to modulate juvenile hormone signaling. J Biol Chem 289: 27874–27885. doi: 10.1074/jbc.M114.582825 25122763

19. He Q, Zhang Y, Zhang X, Xu D, Dong W, et al. (2017) Nucleoporin Nup358 facilitates nuclear import of Methoprene-tolerant (Met) in an importin beta- and Hsp83-dependent manner. Insect Biochem Mol Biol 81: 10–18. doi: 10.1016/j.ibmb.2016.12.005 27979731

20. Liu P, Peng HJ, Zhu J (2015) Juvenile hormone-activated phospholipase C pathway enhances transcriptional activation by the methoprene-tolerant protein. Proc Natl Acad Sci USA 112: E1871–1879. doi: 10.1073/pnas.1423204112 25825754

21. Ojani R, Liu P, Fu X, Zhu J (2016) Protein kinase C modulates transcriptional activation by the juvenile hormone receptor methoprene-tolerant. Insect Biochem Mol Biol 70: 44–52. doi: 10.1016/j.ibmb.2015.12.001 26689644

22. Saha TT, Shin SW, Dou W, Roy S, Zhao B, et al. (2016) Hairy and Groucho mediate the action of juvenile hormone receptor Methoprene-tolerant in gene repression. Proc Natl Acad Sci USA 113: E735–743. doi: 10.1073/pnas.1523838113 26744312

23. Ojani R, Fu X, Ahmed T, Liu P, Zhu J (2018) Krüppel homologue 1 acts as a repressor and an activator in the transcriptional response to juvenile hormone in adult mosquitoes. Insect Mol Biol 27: 268–278. doi: 10.1111/imb.12370 29314423

24. Zhao B, Hou Y, Wang J, Kokoza VA, Saha TT, et al. (2016) Determination of juvenile hormone titers by means of LC-MS/MS/MS and a juvenile hormone-responsive Gal4/UAS system in Aedes aegypti mosquitoes. Insect Biochem Mol Biol 77: 69–77. doi: 10.1016/j.ibmb.2016.08.003 27530057

25. Pecasse F, Beck Y, Ruiz C, Richards G (2000) Krüppel-homolog, a stage-specific modulator of the prepupal ecdysone response, is essential for Drosophila metamorphosis. Dev Biol 221: 53–67. doi: 10.1006/dbio.2000.9687 10772791

26. Minakuchi C, Zhou X, Riddiford LM (2008) Krüppel homolog 1 (Kr-h1) mediates juvenile hormone action during metamorphosis of Drosophila melanogaster. Mech Dev 125: 91–105. doi: 10.1016/j.mod.2007.10.002 18036785

27. Minakuchi C, Namiki T, Shinoda T (2009) Krüppel homolog 1, an early juvenile hormone-response gene downstream of Methoprene-tolerant, mediates its anti-metamorphic action in the red flour beetle Tribolium castaneum. Dev Biol 325: 341–350. doi: 10.1016/j.ydbio.2008.10.016 19013451

28. Bellés X, Santos CG (2014) The MEKRE93 (Methoprene tolerant-Krüppel homolog 1-E93) pathway in the regulation of insect metamorphosis, and the homology of the pupal stage. Insect Biochem Mol Biol 52: 60–68. doi: 10.1016/j.ibmb.2014.06.009 25008785

29. Ureña E, Manjón C, Franch-Marro X, Martín D (2014) Transcription factor E93 specifies adult metamorphosis in hemimetabolous and holometabolous insects. Proc Natl Acad Sci USA 111: 7024–7029. doi: 10.1073/pnas.1401478111 24778249

30. Kayukawa T, Nagamine K, Ito Y, Nishita Y, Ishikawa Y, et al. (2016) Krüppel homolog 1 inhibits insect metamorphosis via direct transcriptional repression of Broad-Complex, a pupal specifier gene. J Biol Chem 291: 1751–1762. doi: 10.1074/jbc.M115.686121 26518872

31. Ureña E, Chafino S, Manjón C, Franch-Marro X, Martín D (2016) The occurrence of the holometabolous pupal stage requires the interaction between E93, Krüppel-Homolog 1 and Broad-Complex. PLoS Genet 12: e1006020. doi: 10.1371/journal.pgen.1006020 27135810

32. Kayukawa T, Jouraku A, Ito Y, Shinoda T (2017) Molecular mechanism underlying juvenile hormone-mediated repression of precocious larval–adult metamorphosis. Proc Natl Acad Sci USA 114: 1057–1062. doi: 10.1073/pnas.1615423114 28096379

33. Zhang Y, Malone JH, Powell SK, Periwal V, Spana E, et al. (2010) Expression in aneuploid Drosophila S2 cells. PLoS Biol 8: e1000320. doi: 10.1371/journal.pbio.1000320 20186269

34. Wang X, Hou Y, Saha TT, Pei G, Raikhel AS, et al. (2017) Hormone and receptor interplay in the regulation of mosquito lipid metabolism. Proc Natl Acad Sci USA 114: E2709–E2718. doi: 10.1073/pnas.1619326114 28292900

35. Roy S, Saha TT, Zou Z, Raikhel AS (2018) Regulatory pathways controlling female insect reproduction. Annu Rev Entomol 63: 489–511. doi: 10.1146/annurev-ento-020117-043258 29058980

36. Song J, Wu Z, Wang Z, Deng S, Zhou S (2014) Krüppel-homolog 1 mediates juvenile hormone action to promote vitellogenesis and oocyte maturation in the migratory locust. Insect Biochem Mol Biol 52: 94–101. doi: 10.1016/j.ibmb.2014.07.001 25017142

37. Parthasarathy R, Sheng Z, Sun Z, Palli SR (2010) Ecdysteroid regulation of ovarian growth and oocyte maturation in the red flour beetle, Tribolium castaneum. Insect Biochem Mol Biol 40: 429–439. doi: 10.1016/j.ibmb.2010.04.002 20385235

38. Smykal V, Bajgar A, Provaznik J, Fexova S, Buricova M, et al. (2014) Juvenile hormone signaling during reproduction and development of the linden bug, Pyrrhocoris apterus. Insect Biochem Mol Biol 45: 69–76. doi: 10.1016/j.ibmb.2013.12.003 24361539

39. Kawata Y, Suzuki H, Higaki Y, Denisenko O, Schullery D, et al. (2002) bcn-1 Element-dependent activation of the laminin gamma 1 chain gene by the cooperative action of transcription factor E3 (TFE3) and Smad proteins. J Biol Chem 277: 11375–11384. doi: 10.1074/jbc.M111284200 11801598

40. Morin S, Pozzulo G, Robitaille L, Cross J, Nemer M (2005) MEF2-dependent recruitment of the HAND1 transcription factor results in synergistic activation of target promoters. J Biol Chem 280: 32272–32278. doi: 10.1074/jbc.M507640200 16043483

41. Nakayama K (2013) cAMP-response element-binding protein (CREB) and NF-κB transcription factors are activated during prolonged hypoxia and cooperatively regulate the induction of matrix metalloproteinase MMP1. J Biol Chem 288: 22584–22595. doi: 10.1074/jbc.M112.421636 23775082

42. Perez-Pinera P, Ousterout DG, Brunger JM, Farin AM, Glass KA, et al. (2013) Synergistic and tunable human gene activation by combinations of synthetic transcription factors. Nat Methods 10: 239–242. doi: 10.1038/nmeth.2361 23377379

43. Delesque-Touchard N, Park SH, Waxman DJ (2000) Synergistic action of hepatocyte nuclear factors 3 and 6 on CYP2C12 gene expression and suppression by growth hormone-activated STAT5b. Proposed model for female specific expression of CYP2C12 in adult rat liver. J Biol Chem 275: 34173–34182. doi: 10.1074/jbc.M004027200 10931833

44. He X, Samee MA, Blatti C, Sinha S (2010) Thermodynamics-based models of transcriptional regulation by enhancers: the roles of synergistic activation, cooperative binding and short-range repression. PloS Comput Biol 6: e1000935. doi: 10.1371/journal.pcbi.1000935 20862354

45. Shao J, Yang VW, Sheng H (2008) Prostaglandin E2 and Krüppel-like transcription factors synergistically induce the expression of decay-accelerating factor in intestinal epithelial cells. Immunology 125: 397–407. doi: 10.1111/j.1365-2567.2008.02847.x 18435741

46. Banerjee N, Zhang MQ (2003) Identifying cooperativity among transcription factors controlling the cell cycle in yeast. Nucleic Acids Res 31: 7024–7031. doi: 10.1093/nar/gkg894 14627835

47. Webber JL, Zhang J, Massey A, Sanchez-Luege N, Rebay I (2018) Collaborative repressive action of the antagonistic ETS transcription factors Pointed and Yan fine-tunes gene expression to confer robustness in Drosophila. Development 145: 165985.

48. Kazemian M, Pham H, Wolfe SA, Brodsky MH, Sinha S (2013) Widespread evidence of cooperative DNA binding by transcription factors in Drosophila development. Nucleic Acids Res 41: 8237–8252. doi: 10.1093/nar/gkt598 23847101

49. Roy SG, Hansen IA, Raikhel AS (2007) Effect of insulin and 20-hydroxyecdysone in the fat body of the yellow fever mosquito, Aedes aegypti. Insect Biochem Mol Biol 37: 1317–1326. doi: 10.1016/j.ibmb.2007.08.004 17967350

50. Powell S, Szklarczyk D, Trachana K, Roth A, Kuhn M, et al. (2012) eggNOG v3.0: orthologous groups covering 1133 organisms at 41 different taxonomic ranges. Nucleic Acids Res 40: D284–D289. doi: 10.1093/nar/gkr1060 22096231

51. Hansen IA, Attardo GM, Roy SG, Raikhel AS (2005) Target of rapamycin-dependent activation of S6 kinase is a central step in the transduction of nutritional signals during egg development in a mosquito. J Biol Chem 280: 20565–20572. doi: 10.1074/jbc.M500712200 15788394