Distinct DNA Binding Sites Contribute to the TCF Transcriptional Switch in and

English version České info

Regulation of gene expression by signaling pathways often occurs through a transcriptional switch, where the transcription factor responsible for signal-dependent gene activation represses the same targets in the absence of signaling. T-cell factors (TCFs) are transcription factors in the Wnt/ß-catenin pathway, which control numerous cell fate specification events in metazoans. The TCF transcriptional switch is mediated by many co-regulators that contribute to repression or activation of Wnt target genes. It is typically assumed that DNA recognition by TCFs is important for target gene location, but plays no role in the actual switch. TCF/Pangolin (the fly TCF) and some vertebrate TCF isoforms bind DNA through two distinct domains, a High Mobility Group (HMG) domain and a C-clamp, which recognize DNA motifs known as HMG and Helper sites, respectively. Here, we demonstrate that POP-1 (the C. elegans TCF) also activates target genes through HMG and Helper site interactions. Helper sites enhanced the ability of a synthetic enhancer to detect Wnt/ß-catenin signaling in several tissues and revealed an unsuspected role for POP-1 in regulating the C. elegans defecation cycle. Searching for HMG-Helper site clusters allowed the identification of a new POP-1 target gene active in the head muscles and gut. While Helper sites and the C-clamp are essential for activation of worm and fly Wnt targets, they are dispensable for TCF-dependent repression of targets in the absence of Wnt signaling. These data suggest that a fundamental change in TCF-DNA binding contributes to the transcriptional switch that occurs upon Wnt stimulation.

Vyšlo v časopise: Distinct DNA Binding Sites Contribute to the TCF Transcriptional Switch in and. PLoS Genet 10(2): e32767. doi:10.1371/journal.pgen.1004133
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004133

Souhrn

Zdroje

1. BaroloS, PosakonyJW (2002) Three habits of highly effective signaling pathways: principles of transcriptional control by developmental cell signaling. Genes Dev 16 : 1167–1181.

2. Bray S, Bernard F (2010) Notch Targets and Their Regulation. In: Raphael K, editor. Current Topics in Developmental Biology: Academic Press. pp. 253–275.

3. BaniahmadA (2005) Nuclear hormone receptor co-repressors. J Steroid Biochem Mol Biol 93 : 89–97.

4. MorelV, LecourtoisM, MassianiO, MaierD, PreissA, et al. (2001) Transcriptional repression by suppressor of hairless involves the binding of a hairless-dCtBP complex in Drosophila. Curr Biol 11 : 789–792.

5. HalfonMS, CarmenaA, GisselbrechtS, SackersonCM, JiménezF, et al. (2000) Ras Pathway Specificity Is Determined by the Integration of Multiple Signal-Activated and Tissue-Restricted Transcription Factors. Cell 103 : 63–74.

6. GhislettiS, HuangW, JepsenK, BennerC, HardimanG, et al. (2009) Cooperative NCoR/SMRT interactions establish a corepressor-based strategy for integration of inflammatory and anti-inflammatory signaling pathways. Genes Dev 23 : 681–693.

7. CadiganKM (2012) TCFs and Wnt/β-catenin signaling: more than one way ot throw the switch. Transcriptional Switches during Development 98 : 1–34.

8. GrigoryanT, WendP, KlausA, BirchmeierW (2008) Deciphering the function of canonical Wnt signals in development and disease: conditional loss -⁠ and gain-of-function mutations of beta-catenin in mice. Genes Dev 22 : 2308–2341.

9. ArchboldHC, YangYX, ChenL, CadiganKM (2012) How do they do Wnt they do?: regulation of transcription by the Wnt/β-catenin pathway. Acta Physiologica 204 : 74–109.

10. PolakisP (2012) Wnt signaling in cancer. Cold Spring Harb Perspect Biol 4: a008052.

11. CadiganKM, WatermanML (2012) TCF/LEFs and Wnt signaling in the nucleus. Cold Spring Harb Perspect Biol 4: a007906.

12. CadiganKM, PeiferM (2009) Wnt signaling from development to disease: insights from model systems. Cold Spring Harb Perspect Biol 1: a002881.

13. MacDonaldBT, TamaiK, HeX (2009) Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell 17 : 9–26.

14. ValentaT, HausmannG, BaslerK (2012) The many faces and functions of β-catenin. EMBO J 31 : 2714–2736.

15. MaduroMF, KasmirJJ, ZhuJ, RothmanJH (2005) The Wnt effector POP-1 and the PAL-1/Caudal homeoprotein collaborate with SKN-1 to activate C. elegans endoderm development. Dev Biol 285 : 510–523.

16. ShettyP, LoMC, RobertsonSM, LinRL (2005) C-elegans TCF protein, POP-1, converts from repressor to activator as a result of Wnt-induced lowering of nuclear levels. Developmental Biology 285 : 584–592.

17. MaduroMF, Broitman-MaduroG, MengarelliI, RothmanJH (2007) Maternal deployment of the embryonic SKN-1→MED-1,2 cell specification pathway in C. elegans. Dev Biol 301 : 590–601.

18. HuangSY, ShettyP, RobertsonSM, LinR (2007) Binary cell fate specification during C-elegans embryogenesis driven by reiterated reciprocal asymmetry of TCF POP-1 and its coactivator beta-catenin SYS-1. Development 134 : 2685–2695.

19. LinR, ThompsonS, PriessJR (1995) pop-1 encodes an HMG box protein required for the specification of a mesoderm precursor in early C. elegans embryos. Cell 83 : 599–609.

20. MaduroMF, LinR, RothmanJH (2002) Dynamics of a developmental switch: recursive intracellular and intranuclear redistribution of Caenorhabditis elegans POP-1 parallels Wnt-inhibited transcriptional repression. Dev Biol 248 : 128–142.

21. LinKT, Broitman-MaduroG, HungWW, CervantesS, MaduroMF (2009) Knockdown of SKN-1 and the Wnt effector TCF/POP-1 reveals differences in endomesoderm specification in C. briggsae as compared with C. elegans. Dev Biol 325 : 296–306.

22. OwraghiM, Broitman-MaduroG, LuuT, RobersonH, MaduroMF (2010) Roles of the Wnt effector POP-1/TCF in the C. elegans endomesoderm specification gene network. Dev Biol 340 : 209–221.

23. RobertsonSM, LoMC, OdomR, YangXD, MedinaJ, et al. (2011) Functional analyses of vertebrate TCF proteins in C. elegans embryos. Dev Biol 355 : 115–123.

24. CavalloRA, CoxRT, MolineMM, RooseJ, PolevoyGA, et al. (1998) Drosophila Tcf and Groucho interact to repress Wingless signalling activity. Nature 395 : 604–608.

25. SchweizerL, NellenD, BaslerK (2003) Requirement for Pangolin/dTCF in Drosophila Wingless signaling. Proc Natl Acad Sci U S A 100 : 5846–5851.

26. RieseJ, YuX, MunnerlynA, EreshS, HsuSC, et al. (1997) LEF-1, a nuclear factor coordinating signaling inputs from wingless and decapentaplegic. Cell 88 : 777–787.

27. KnirrS, FraschM (2001) Molecular integration of inductive and mesoderm-intrinsic inputs governs even-skipped enhancer activity in a subset of pericardial and dorsal muscle progenitors. Dev Biol 238 : 13–26.

28. YangX, van BeestM, CleversH, JonesT, HurshDA, et al. (2000) decapentaplegic is a direct target of dTcf repression in the Drosophila visceral mesoderm. Development 127 : 3695–3702.

29. CalvoD, VictorM, GayF, SuiG, LukeMP, et al. (2001) A POP-1 repressor complex restricts inappropriate cell type-specific gene transcription during Caenorhabditis elegans embryogenesis. EMBO J 20 : 7197–7208.

30. PhillipsBT, KimbleJ (2009) A New Look at TCF and beta-Catenin through the Lens of a Divergent C-elegans Wnt Pathway. Developmental Cell 17 : 27–34.

31. JacksonBM, EisenmannDM (2012) beta-catenin-dependent Wnt signaling in C. elegans: teaching an old dog a new trick. Cold Spring Harb Perspect Biol 4: a007948.

32. SawaH (2012) Control of cell polarity and asymmetric division in C. elegans. Transcriptional Switches during Development 101 : 55–76.

33. MeneghiniMD, IshitaniT, CarterJC, HisamotoN, Ninomiya-TsujiJ, et al. (1999) MAP kinase and Wnt pathways converge to downregulate an HMG-domain repressor in Caenorhabditis elegans. Nature 399 : 793–797.

34. RocheleauCE, YasudaJ, ShinTH, LinRL, SawaH, et al. (1999) WRM-1 activates the LIT-1 protein kinase to transduce anterior posterior polarity signals in C-elegans. Cell 97 : 717–726.

35. ShinTH, YasudaJ, RocheleauCE, LinRL, SotoM, et al. (1999) MOM-4, a MAP kinase kinase kinase-related protein, activates WRM-1/LIT-1 kinase to transduce anterior/posterior polarity signals in C-elegans. Molecular Cell 4 : 275–280.

36. LoMC, GayF, OdomR, ShiY, LinF (2004) Phosphorylation by the beta-catenin/MAPK complex promotes 14-3-3-mediated nuclear export of TCF/POP-1 in signal-responsive cells in C-elegans. Cell 117 : 95–106.

37. van de WeteringM, CavalloR, DooijesD, van BeestM, van EsJ, et al. (1997) Armadillo coactivates transcription driven by the product of the Drosophila segment polarity gene dTCF. Cell 88 : 789–799.

38. HallikasO, PalinK, SinjushinaN, RautiainenR, PartanenJ, et al. (2006) Genome-wide prediction of mammalian enhancers based on analysis of transcription-factor binding affinity. Cell 124 : 47–59.

39. AtchaFA, SyedA, WuB, HoverterNP, YokoyamaNN, et al. (2007) A unique DNA binding domain converts T-cell factors into strong Wnt effectors. Mol Cell Biol 27 : 8352–8363.

40. ChangMV, ChangJL, GangopadhyayA, ShearerA, CadiganKM (2008) Activation of wingless targets requires bipartite recognition of DNA by TCF. Curr Biol 18 : 1877–1881.

41. HoverterNP, TingJH, SundareshS, BaldiP, WatermanML (2012) A WNT/p21 circuit directed by the C-clamp, a sequence-specific DNA binding domain in TCFs. Mol Cell Biol 32 : 3648–3662.

42. LamN, ChesneyMA, KimbleJ (2006) Wnt signaling and CEH-22/tinman/Nkx2.5 specify a stem cell niche in C-elegans. Current Biology 16 : 287–295.

43. ArataY, KouikeH, ZhangYP, HermanMA, OkanoH, et al. (2006) Wnt signaling and a Hox protein cooperatively regulate PSA-3/Meis to determine daughter cell fate after asymmetric cell division in C-elegans. Developmental Cell 11 : 105–115.

44. KimbleJE, WhiteJG (1981) On the control of germ cell development in Caenorhabditis elegans. Developmental Biology 81 : 208–219.

45. SosinskyA, BoninCP, MannRS, HonigB (2003) Target Explorer: an automated tool for the identification of new target genes for a specified set of transcription factors. Nucleic Acids Research 31 : 3589–3592.

46. GaudetJ, MuttumuS, HornerM, MangoSE (2004) Whole-genome analysis of temporal gene expression during foregut development. Plos Biology 2: e352.

47. Hunt-NewburyR, ViveirosR, JohnsenR, MahA, AnastasD, et al. (2007) High-throughput in vivo analysis of gene expression in Caenorhabditis elegans. Plos Biology 5 : 1981–1997.

48. DupuyD, BertinN, HidalgoCA, VenkatesanK, TuD, et al. (2007) Genome-scale analysis of in vivo spatiotemporal promoter activity in Caenorhabditis elegans. Nature Biotechnology 25 : 663–668.

49. SleumerMC, BilenkyM, HeA, RobertsonG, ThiessenN, et al. (2009) Caenorhabditis elegans cisRED: a catalogue of conserved genomic elements. Nucleic Acids Research 37 : 1323–1334.

50. SiegfriedKR, KimbleJ (2002) POP-1 controls axis formation during early gonadogenesis in C-elegans. Development 129 : 443–453.

51. KamathRS, AhringerJ (2003) Genome-wide RNAi screening in Caenorhabditis elegans. Methods 30 : 313–321.

52. BaroloS (2006) Transgenic Wnt/TCF pathway reporters: all you need is Lef? Oncogene 25 : 7505–7511.

53. KorinekV, BarkerN, MorinPJ, van WichenD, de WegerR, et al. (1997) Constitutive Transcriptional Activation by a β-Catenin-Tcf Complex in APC−/ −⁠ Colon Carcinoma. Science 275 : 1784–1787.

54. DasGuptaR, FuchsE (1999) Multiple roles for activated LEF/TCF transcription complexes during hair follicle development and differentiation. Development 126 : 4557–4568.

55. GreenJL, InoueT, SternbergPW (2008) Opposing Wnt pathways orient cell polarity during organogenesis. Cell 134 : 646–656.

56. TeramotoT, IwasakiK (2006) Intestinal calcium waves coordinate a behavioral motor program in C. elegans. Cell Calcium 40 : 319–327.

57. ThomasJH (1990) Genetic analysis of defecation in Caenorhabditis elegans. Genetics 124 : 855–872.

58. Dal SantoP, LoganMA, ChisholmAD, JorgensenEM (1999) The inositol trisphosphate receptor regulates a 50-second behavioral rhythm in C. elegans. Cell 98 : 757–767.

59. EspeltMV, EstevezAY, YinX, StrangeK (2005) Oscillatory Ca2+ signaling in the isolated Caenorhabditis elegans intestine: role of the inositol-1,4,5-trisphosphate receptor and phospholipases C beta and gamma. J Gen Physiol 126 : 379–392.

60. WangH, GirskisK, JanssenT, ChanJP, DasguptaK, et al. (2013) Neuropeptide secreted from a pacemaker activates neurons to control a rhythmic behavior. Curr Biol 23 : 746–754.

61. LinRL, HillRJ, PriessJR (1998) POP-1 and anterior-posterior fate decisions in C-elegans embryos. Cell 92 : 229–239.

62. KingRS, MaidenSL, HawkinsNC, KiddAR, KimbleJ, et al. (2009) The N -⁠ or C-terminal domains of DSH-2 can activate the C. elegans Wnt/beta-catenin asymmetry pathway. Developmental Biology 328 : 234–244.

63. GleasonJE, KorswagenHC, EisenmannDM (2002) Activation of Wnt signaling bypasses the requirement for RTK/Ras signaling during C-elegans vulval induction. Genes & Development 16 : 1281–1290.

64. KorswagenHC, CoudreuseDYM, BetistMC, van de WaterS, ZivkovicD, et al. (2002) The Axin-like protein PRY-1 is a negative regulator of a canonical Wnt pathway in C-elegans. Genes & Development 16 : 1291–1302.

65. McGheeJD, FukushigeT, KrauseMW, MinnemaSE, GoszczynskiB, et al. (2009) ELT-2 is the predominant transcription factor controlling differentiation and function of the C. elegans intestine, from embryo to adult. Developmental Biology 327 : 551–565.

66. PilipiukJ, LefebvreC, WiesenfahrtT, LegouisR, BossingerO (2009) Increased IP3/Ca2+ signaling compensates depletion of LET-413/DLG-1 in C. elegans epithelial junction assembly. Developmental Biology 327 : 34–47.

67. PhillipsRG, WhittleJR (1993) wingless expression mediates determination of peripheral nervous system elements in late stages of Drosophila wing disc development. Development 118 : 427–438.

68. CousoJP, BishopSA, Martinez AriasA (1994) The wingless signalling pathway and the patterning of the wing margin in Drosophila. Development 120 : 621–636.

69. BlairSS (1992) Shaggy (zeste-white 3) and the formation of supernumerary bristle precursors in the developing wing blade of Drosophila. Dev Biol 152 : 263–278.

70. CadiganKM, FishMP, RulifsonEJ, NusseR (1998) Wingless repression of Drosophila frizzled 2 expression shapes the Wingless morphogen gradient in the wing. Cell 93 : 767–777.

71. KruppJJ, YaichLE, WessellsRJ, BodmerR (2005) Identification of genetic loci that interact with cut during Drosophila wing-margin development. Genetics 170 : 1775–1795.

72. DietzlG, ChenD, SchnorrerF, SuKC, BarinovaY, et al. (2007) A genome-wide transgenic RNAi library for conditional gene inactivation in Drosophila. Nature 448 : 151–156.

73. PhillipsBT, KiddAR, KingR, HardinJ, KimbleJ (2007) Reciprocal asymmetry of SYS-1/beta-catenin and POP-1/TCF controls asymmetric divisions in Caenorhabditis elegans. Proceedings of the National Academy of Sciences of the United States of America 104 : 3231–3236.

74. HuangL, LiX, El-HodiriHM, DayalS, WikramanayakeAH, et al. (2000) Involvement of Tcf/Lef in establishing cell types along the animal-vegetal axis of sea urchins. Dev Genes Evol 210 : 73–81.

75. AdamskaM, LarrouxC, AdamskiM, GreenK, LovasE, et al. (2010) Structure and expression of conserved Wnt pathway components in the demosponge Amphimedon queenslandica. Evol Dev 12 : 494–518.

76. DuffyDJ, PlickertG, KuenzelT, TilmannW, FrankU (2010) Wnt signaling promotes oral but suppresses aboral structures in Hydractinia metamorphosis and regeneration. Development 137 : 3057–3066.

77. KorswagenHC, HermanMA, CleversHC (2000) Distinct beta-catenins mediate adhesion and signalling functions in C-elegans. Nature 406 : 527–532.

78. Reece-HoyesJS, ShinglesJ, DupuyD, GroveCA, WalhoutAJM, et al. (2007) Insight into transcription factor gene duplication from Caenorhabditis elegans promoterome-driven expression patterns. BMC Genomics 8 : 27.

79. HunterCP, HarrisJM, MaloofJN, KenyonC (1999) Hox gene expression in a single Caenorhabditis elegans cell is regulated by a caudal homolog and intercellular signals that inhibit Wnt signaling. Development 126 : 805–814.

80. MaloofJN, WhangboJ, HarrisJM, JongewardGD, KenyonC (1999) A Wnt signaling pathway controls Hox gene expression and neuroblast migration in C-elegans. Development 126 : 37–49.

81. EisenmannDM, MaloofJN, SimskeJS, KenyonC, KimSK (1998) The beta-catenin homolog BAR-1 and LET-60 Ras coordinately regulate the Hox gene lin-39 during Caenorhabditis elegans vulval development. Development 125 : 3667–3680.

82. HermanMA (2001) C-elegans POP-1/TCF functions in a canonical Wnt pathway that controls cell migration acid in a noncanonical Wnt pathway that controls cell polarity. Development 128 : 581–590.

83. HornerMA, QuintinS, DomeierME, KimbleJ, LabouesseM, et al. (1998) pha-4, an HNF-3 homolog, specifies pharyngeal organ identity in Caenorhabditis elegans. Genes & Development 12 : 1947–1952.

84. MangoSE, LambieEJ, KimbleJ (1994) The Pha-4 Gene Is Required to Generate the Pharyngeal Primordium of Caenorhabditis-Elegans. Development 120 : 3019–3031.

85. MurrayJI, BoyleTJ, PrestonE, VafeadosD, MericleB, et al. (2012) Multidimensional regulation of gene expression in the C. elegans embryo. Genome Research 22 : 1282–1294.

86. GorrepatiL, ThompsonKW, EisenmannDM (2013) C. elegans GATA factors EGL-18 and ELT-6 function downstream of Wnt signaling to maintain the progenitor fate during larval asymmetric divisions of the seam cells. Development 140 : 2093–2102.

87. SokolSY (2011) Wnt signaling through T-cell factor phosphorylation. Cell Research 21 : 1002–1012.

88. WuC-I, HoffmanJA, ShyBR, FordEM, FuchsE, et al. (2012) Function of Wnt/β-catenin in counteracting Tcf3 repression through the Tcf3–β-catenin interaction. Development 139 : 2118–2129.

89. ChangJL, LinHV, BlauwkampTA, CadiganKM (2008) Spenito and Split ends act redundantly to promote Wingless signaling. Developmental Biology 314 : 100–111.

90. FangM, LiJ, BlauwkampT, BhambhaniC, CampbellN, et al. (2006) C-terminal-binding protein directly activates and represses Wnt transcriptional targets in Drosophila. Embo Journal 25 : 2735–2745.

91. LiJ, SutterC, ParkerDS, BlauwkampT, FangM, et al. (2007) CBP/p300 are bimodal regulators of Wnt signaling. Embo Journal 26 : 2284–2294.

92. ParkerDS, NiYYY, ChangJHL, LiJ, CadiganKM (2008) Wingless signaling induces widespread chromatin remodeling of target loci. Molecular and Cellular Biology 28 : 1815–1828.

93. SierraJ, YoshidaT, JoazeiroCA, JonesKA (2006) The APC tumor suppressor counteracts beta-catenin activation and H3K4 methylation at Wnt target genes. Genes & Development 20 : 586–600.

94. MahonyS, MazzoniEO, McCuineS, YoungRA, WichterleH, et al. (2011) Ligand-dependent dynamics of retinoic acid receptor binding during early neurogenesis. Genome Biology 12: R2.

95. KrejciA, BrayS (2007) Notch activation stimulates transient and selective binding of Su(H)/CSL to target enhancers. Genes & Development 21 : 1322–1327.

96. ArnettKL, HassM, McArthurDG, IlaganMXG, AsterJC, et al. (2010) Structural and mechanistic insights into cooperative assembly of dimeric Notch transcription complexes. Nature Structural & Molecular Biology 17 : 1312–1317.

97. BranickyR, HekimiS (2006) What keeps C-elegans regular: the genetics of defecation. Trends in Genetics 22 : 571–579.

98. HarterinkM, KimDH, MiddelkoopTC, DoanTD, van OudenaardenA, et al. (2011) Neuroblast migration along the anteroposterior axis of C. elegans is controlled by opposing gradients of Wnts and a secreted Frizzled-related protein. Development 138 : 2915–2924.

99. CoudreuseDY, RoelG, BetistMC, DestreeO, KorswagenHC (2006) Wnt gradient formation requires retromer function in Wnt-producing cells. Science 312 : 921–924.

100. LacknerMR, NurrishSJ, KaplanJM (1999) Facilitation of synaptic transmission by EGL-30 G(q)alpha and EGL-8 PLC beta: DAG binding to UNC-13 is required to stimulate acetylcholine release. Neuron 24 : 335–346.

101. SulstonJE, HorvitzHR (1977) Post-embryonic cell lineages of the nematode, Caenorhabditis elegans. Dev Biol 56 : 110–156.

102. SulstonJE, SchierenbergE, WhiteJG, ThomsonJN (1983) The embryonic cell lineage of the nematode Caenorhabditis elegans. Dev Biol 100 : 64–119.

103. Crittenden S, Kimble J (2009) Preparation and immunolabeling of Caenorhabditis elegans. Cold Spring Harb Protoc 2009: pdb prot5216.

104. BhambhaniC, ChangJL, AkeyDL, CadiganKM (2011) The oligomeric state of CtBP determines its role as a transcriptional co-activator and co-repressor of Wingless targets. Embo Journal 30 : 2031–2043.

105. BranickyR, ShibataY, FengJL, HekimiS (2001) Phenotypic and suppressor analysis of defecation in clk-1 mutants reveals that reaction to changes in temperature is an active process in Caenorhabditis elegans. Genetics 159 : 997–1006.

106. ColletteKS, PettyEL, GolenbergN, BembenekJN, CsanskovszkiG (2011) Different roles for Aurora B in condensin targeting during mitosis and meiosis. Journal Cell Science 124 : 3684–3694.

107. HermanMA, HorvitzHR (1994) The Caenorhabditis elegans gene lin-44 controls the polarity of asymmetric cell divisions. Development 120 : 1035–1047.