Non-coding RNAs Prevent the Binding of the MSL-complex to Heterochromatic Regions

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In both fruit flies and humans, males and females have different sets of sex chromosomes. This generates differences in gene dosage that must be compensated for by adjusting the transcriptional output of most genes located on the X-chromosome. The specific recognition and targeting of the X-chromosome is essential for such dosage compensation. In fruit flies, dosage compensation is mediated by the male-specific lethal (MSL) complex, which upregulates gene transcription on the male X-chromosome. The MSL-complex consists of five proteins and two non-coding RNAs, roX1 and roX2. While non-coding RNAs are known to be critical for dosage compensation in both flies and mammals, their precise functions remain elusive. Here we present a study on the targeting and function of the MSL-complex in the absence of roX RNAs. The results obtained suggest that the dosage compensating MSL-complex has an intrinsic tendency to target repeat-rich regions and that the function of roX RNAs is to prevent its binding to such targets. Our findings reveal an ancient targeting and regulatory function of the MSL-complex that has been adapted for use in dosage compensation and modified by the rapidly evolving noncoding roX RNAs.

Vyšlo v časopise: Non-coding RNAs Prevent the Binding of the MSL-complex to Heterochromatic Regions. PLoS Genet 10(12): e32767. doi:10.1371/journal.pgen.1004865
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004865

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Zdroje

1. StenbergP, LarssonJ (2011) Buffering and the evolution of chromosome-wide gene regulation. Chromosoma 120: 213–225.

2. VicosoB, BachtrogD (2009) Progress and prospects toward our understanding of the evolution of dosage compensation. Chromosome Res 17: 585–602.

3. MankJE (2013) Sex chromosome dosage compensation: definitely not for everyone. Trends Genet 29: 677–683.

4. StenbergP, LundbergLE, JohanssonAM, RydénP, SvenssonMJ, et al. (2009) Buffering of segmental and chromosomal aneuploidies in Drosophila melanogaster. PLoS Genet 5: e100302.

5. LundbergLE, FigueiredoML, StenbergP, LarssonJ (2012) Buffering and proteolysis are induced by segmental monosomy in Drosophila melanogaster. Nucleic Acids Res 40: 5926–5937.

6. ZhangY, MaloneJH, PowellSK, PeriwalV, SpanaE, et al. (2010) Expression in aneuploid Drosophila S2 cells. PLoS Biol 8: e1000320.

7. PrestelM, FellerC, BeckerPB (2010) Dosage compensation and the global re-balancing of aneuploid genomes. Genome Biol 11: 216.

8. GelbartME, KurodaMI (2009) Drosophila dosage compensation: a complex voyage to the X chromosome. Development 136: 1399–1410.

9. ConradT, AkhtarA (2011) Dosage compensation in Drosophila melanogaster: epigenetic fine-tuning of chromosome-wide transcription. Nat Rev Genet 13: 123–134.

10. GelbartME, LarschanE, PengS, ParkPJ, KurodaMI (2009) Drosophila MSL complex globally acetylates H4K16 on the male X chromosome for dosage compensation. Nat Struct Mol Biol 16: 825–832.

11. Shogren-KnaakM, IshiiH, SunJM, PazinMJ, DavieJR, et al. (2006) Histone H4-K16 acetylation controls chromatin structure and protein interactions. Science 311: 844–847.

12. BashawGJ, BakerBS (1995) The msl-2 dosage compensation gene of Drosophila encodes a putative DNA-binding protein whose expression is sex specifically regulated by Sex-lethal. Development 121: 3245–3258.

13. KelleyRL, SolovyevaI, LymanLM, RichmanR, SolovyevV, et al. (1995) Expression of msl-2 causes assembly of dosage compensation regulators on the X chromosomes and female lethality in Drosophila. Cell 81: 867–877.

14. ZhouS, YangY, ScottMJ, PannutiA, FehrKC, et al. (1995) Male-specific lethal 2, a dosage compensation gene of Drosophila, undergoes sex-specific regulation and encodes a protein with a RING finger and a metallothionein-like cysteine cluster. EMBO J 14: 2884–2895.

15. MellerVH, WuKH, RomanG, KurodaMI, DavisRL (1997) roX1 RNA paints the X chromosome of male Drosophila and is regulated by the dosage compensation system. Cell 88: 445–457.

16. RattnerBP, MellerVH (2004) Drosophila male-specific lethal 2 protein controls sex-specific expression of the roX genes. Genetics 166: 1825–1832.

17. PhilipP, StenbergP (2013) Male X-linked genes in Drosophila melanogaster are compensated independently of the Male-Specific Lethal complex. Epigenetics Chromatin 6: 35.

18. GuptaV, ParisiM, SturgillD, NuttallR, DoctoleroM, et al. (2006) Global analysis of X-chromosome dosage compensation. J Biol 5: 3.

19. HamadaFN, ParkPJ, GordadzePR, KurodaMI (2005) Global regulation of X chromosomal genes by the MSL complex in Drosophila melanogaster. Genes Dev 19: 2289–2294.

20. DengX, MellerVH (2006) roX RNAs are required for increased expression of X-linked genes in Drosophila melanogaster males. Genetics 174: 1859–1866.

21. BirchlerJA, Pal-BhadraM, BhadraU (2003) Dosage dependent gene regulation and the compensation of the X chromosome in Drosophila males. Genetica 117: 179–190.

22. VeitiaRA, BottaniS, BirchlerJA (2008) Cellular reactions to gene dosage imbalance: genomic, transcriptomic and proteomic effects. Trends Genet 24: 390–397.

23. BirchlerJA (2014) Facts and artifacts in studies of gene expression in aneuploids and sex chromosomes. Chromosoma 123: 459–469.

24. SunL, FernandezHR, DonohueRC, LiJ, ChengJ, et al. (2013) Male-specific lethal complex in Drosophila counteracts histone acetylation and does not mediate dosage compensation. Proc Natl Acad Sci U S A 110: 7383–7388.

25. LymanLM, CoppsK, RastelliL, KelleyRL, KurodaMI (1997) Drosophila male-specific lethal-2 protein: structure/function analysis and dependence on MSL-1 for chromosome association. Genetics 147: 1743–1753.

26. CoppsK, RichmanR, LymanLM, ChangKA, Rampersad-AmmonsJ, et al. (1998) Complex formation by the Drosophila MSL proteins: role of the MSL2 RING finger in protein complex assembly. EMBO J 17: 5409–5417.

27. FauthT, Müller-PlanitzF, KönigC, StraubT, BeckerPB (2010) The DNA binding CXC domain of MSL2 is required for faithful targeting the Dosage Compensation Complex to the X chromosome. Nucleic Acids Res 38: 3209–3221.

28. KelleyRL, LeeOK, ShimYK (2008) Transcription rate of noncoding roX1 RNA controls local spreading of the Drosophila MSL chromatin remodeling complex. Mech Dev 125: 1009–1019.

29. ParkSW, KurodaMI, ParkY (2008) Regulation of histone H4 Lys16 acetylation by predicted alternative secondary structures in roX noncoding RNAs. Mol Cell Biol 28: 4952–4962.

30. ParkSW, KangYIe, SypulaJG, ChoiJ, OhH, et al. (2007) An evolutionarily conserved domain of roX2 RNA is sufficient for induction of H4-Lys16 acetylation on the Drosophila X chromosome. Genetics 177: 1429–1437.

31. IlikIA, QuinnJJ, GeorgievP, Tavares-CadeteF, MaticzkaD, et al. (2013) Tandem stem-loops in roX RNAs act together to mediate X chromosome dosage compensation in Drosophila. Mol Cell 51: 156–173.

32. MaennerS, MüllerM, FröhlichJ, LangerD, BeckerPB (2013) ATP-dependent roX RNA remodeling by the helicase maleless enables specific association of MSL proteins. Mol Cell 51: 174–184.

33. KelleyRL, MellerVH, GordadzePR, RomanG, DavisRL, et al. (1999) Epigenetic spreading of the Drosophila dosage compensation complex from roX RNA genes into flanking chromatin. Cell 98: 513–522.

34. StraubT, ZabelA, GilfillanGD, FellerC, BeckerPB (2013) Different chromatin interfaces of the Drosophila dosage compensation complex revealed by high-shear ChIP-seq. Genome Res 23: 473–485.

35. DahlsveenIK, GilfillanGD, ShelestVI, LammR, BeckerPB (2006) Targeting determinants of dosage compensation in Drosophila. PLoS Genet 2: e5.

36. OhH, BoneJR, KurodaMI (2004) Multiple classes of MSL binding sites target dosage compensation to the X chromosome of Drosophila. Curr Biol 14: 481–487.

37. AlekseyenkoAA, PengS, LarschanE, GorchakovAA, LeeOK, et al. (2008) A sequence motif within chromatin entry sites directs MSL establishment on the Drosophila X chromosome. Cell 134: 599–609.

38. StraubT, GrimaudC, GilfillanGD, MitterwegerA, BeckerPB (2008) The chromosomal high-affinity binding sites for the Drosophila dosage compensation complex. PLoS Genet 4: e1000302.

39. LucchesiJC (1998) Dosage compensation in flies and worms: the ups and downs of X-chromosome regulation. Curr Opin Genet Dev 8: 179–184.

40. SassGL, PannutiA, LucchesiJC (2003) Male-specific lethal complex of Drosophila targets activated regions of the X chromosome for chromatin remodeling. Proc Natl Acad Sci U S A 100: 8287–8291.

41. LarschanE, AlekseyenkoAA, GortchakovAA, PengS, LiB, et al. (2007) MSL complex is attracted to genes marked by H3K36 trimethylation using a sequence-independent mechanism. Mol Cell 28: 121–133.

42. GilfillanGD, StraubT, de WitE, GreilF, LammR, et al. (2006) Chromosome-wide gene-specific targeting of the Drosophila dosage compensation complex. Genes Dev 20: 858–870.

43. AlekseyenkoAA, LarschanE, LaiWR, ParkPJ, KurodaMI (2006) High-resolution ChIP-chip analysis reveals that the Drosophila MSL complex selectively identifies active genes on the male X chromosome. Genes Dev 20: 848–857.

44. LarschanE, AlekseyenkoAA, LaiWR, ParkPJ, KurodaMI (2006) MSL complex associates with clusters of actively transcribed genes along the Drosophila male X chromosome. Cold Spring Harb Symp Quant Biol 71: 385–394.

45. PhilipP, PetterssonF, StenbergP (2012) Sequence signatures involved in targeting the Male-Specific Lethal complex to X-chromosomal genes in Drosophila melanogaster. BMC Genomics 13: 97.

46. LucchesiJC (2009) The structure-function link of compensated chromatin in Drosophila. Curr Opin Genet Dev 19: 550–556.

47. MellerVH, RattnerBP (2002) The roX genes encode redundant male-specific lethal transcripts required for targeting of the MSL complex. EMBO J 21: 1084–1091.

48. JohanssonAM, AllgardssonA, StenbergP, LarssonJ (2011) msl2 mRNA is bound by free nuclear MSL complex in Drosophila melanogaster. Nucleic Acids Res 39: 6428–6439.

49. LoheAR, HillikerAJ, RobertsPA (1993) Mapping simple repeated DNA sequences in heterochromatin of Drosophila melanogaster. Genetics 134: 1149–1174.

50. VicosoB, BachtrogD (2013) Reversal of an ancient sex chromosome to an autosome in Drosophila. Nature 499: 332–335.

51. LarssonJ, MellerVH (2006) Dosage compensation, the origin and the afterlife of sex chromosomes. Chromosome Res 14: 417–431.

52. Hochman B (1976) The fourth chromosome of Drosophila melanogaster. In: Ashburner M, Novitski E, editors. The Genetics and biology of Drosophila: Academic Press. pp. 903–928.

53. JinY, WangY, WalkerDL, DongH, ConleyC, et al. (1999) JIL-1: a novel chromosomal tandem kinase implicated in transcriptional regulation in Drosophila. Mol Cell 4: 129–135.

54. JinY, WangY, JohansenJ, JohansenKM (2000) JIL-1, a chromosomal kinase implicated in regulation of chromatin structure, associates with the male specific lethal (MSL) dosage compensation complex. J Cell Biol 149: 1005–1010.

55. RegnardC, StraubT, MitterwegerA, DahlsveenIK, FabianV, et al. (2011) Global analysis of the relationship between JIL-1 kinase and transcription. PLoS Genet 7: e1001327.

56. WangCI, AlekseyenkoAA, LeroyG, EliaAE, GorchakovAA, et al. (2013) Chromatin proteins captured by ChIP-mass spectrometry are linked to dosage compensation in Drosophila. Nat Struct Mol Biol 20: 202–209.

57. KrivshenkoJD (1955) A cytogenetic study of the X chromosome of Drosophila busckii and its relation to phylogeny. Proc Natl Acad Sci U S A 41: 1071–1079.

58. KrivshenkoJD (1959) New evidence for the homology of the short euchromatic elements of the X and Y chromosomes of Drosophila busckii with the microchromosome of Drosophila melanogaster. Genetics 44: 1027–1040.

59. KapitonovVV, JurkaJ (2003) Molecular paleontology of transposable elements in the Drosophila melanogaster genome. Proc Natl Acad Sci U S A 100: 6569–6574.

60. St PierreSE, PontingL, StefancsikR, McQuiltonP, ConsortiumF (2014) FlyBase 102–advanced approaches to interrogating FlyBase. Nucleic Acids Res 42: D780–788.

61. BachtrogD, WeissS, ZangerlB, BremG, SchlottererC (1999) Distribution of dinucleotide microsatellites in the Drosophila melanogaster genome. Mol Biol Evol 16: 602–610.

62. KattiMV, RanjekarPK, GuptaVS (2001) Differential distribution of simple sequence repeats in eukaryotic genome sequences. Mol Biol Evol 18: 1161–1167.

63. PardueML, LowenhauptK, RichA, NordheimA (1987) (dC-dA)n.(dG-dT)n sequences have evolutionarily conserved chromosomal locations in Drosophila with implications for roles in chromosome structure and function. EMBO J 6: 1781–1789.

64. DorerDR, HenikoffS (1994) Expansions of transgene repeats cause heterochromatin formation and gene silencing in Drosophila. Cell 77: 993–1002.

65. LiY, DanzerJR, AlvarezP, BelmontAS, WallrathLL (2003) Effects of tethering HP1 to euchromatic regions of the Drosophila genome. Development 130: 1817–1824.

66. MaennerS, MüllerM, BeckerPB (2012) Roles of long, non-coding RNA in chromosome-wide transcription regulation: lessons from two dosage compensation systems. Biochimie 94: 1490–1498.

67. FilionGJ, van BemmelJG, BraunschweigU, TalhoutW, KindJ, et al. (2010) Systematic protein location mapping reveals five principal chromatin types in Drosophila cells. Cell 143: 212–224.

68. DengX, RattnerBP, SouterS, MellerVH (2005) The severity of roX1 mutations is predicted by MSL localization on the X chromosome. Mech Dev 122: 1094–1105.

69. MenonDU, MellerVH (2009) Imprinting of the Y chromosome influences dosage compensation in roX1 roX2 Drosophila melanogaster. Genetics 183: 811–820.

70. HoskinsRA, SmithCD, CarlsonJW, CarvalhoAB, HalpernA, et al. (2002) Heterochromatic sequences in a Drosophila whole-genome shotgun assembly. Genome Biol 3: RESEARCH0085.

71. GrimaudC, BeckerPB (2009) The dosage compensation complex shapes the conformation of the X chromosome in Drosophila. Genes Dev 23: 2490–2495.

72. DemakovaOV, KotlikovaIV, GordadzePR, AlekseyenkoAA, KurodaMI, et al. (2003) The MSL complex levels are critical for its correct targeting to the chromosomes in Drosophila melanogaster. Chromosoma 112: 103–115.

73. KharchenkoPV, AlekseyenkoAA, SchwartzYB, MinodaA, RiddleNC, et al. (2011) Comprehensive analysis of the chromatin landscape in Drosophila melanogaster. Nature 471: 480–485.

74. RiddleNC, MinodaA, KharchenkoPV, AlekseyenkoAA, SchwartzYB, et al. (2011) Plasticity in patterns of histone modifications and chromosomal proteins in Drosophila heterochromatin. Genome Res 21: 147–163.

75. YinH, SweeneyS, RahaD, SnyderM, LinH (2011) A high-resolution whole-genome map of key chromatin modifications in the adult Drosophila melanogaster. PLoS Genet 7: e1002380.

76. FigueiredoML, PhilipP, StenbergP, LarssonJ (2012) HP1a recruitment to promoters is independent of H3K9 methylation in Drosophila melanogaster. PLoS Genet 8: e1003061.

77. de WitE, GreilF, van SteenselB (2005) Genome-wide HP1 binding in Drosophila: developmental plasticity and genomic targeting signals. Genome Res 15: 1265–1273.

78. LiuLP, NiJQ, ShiYD, OakeleyEJ, SunFL (2005) Sex-specific role of Drosophila melanogaster HP1 in regulating chromatin structure and gene transcription. Nat Genet 37: 1361–1366.

79. PrestelM, FellerC, StraubT, MitlöhnerH, BeckerPB (2010) The activation potential of MOF is constrained for dosage compensation. Mol Cell 38: 815–826.

80. JohanssonAM, StenbergP, BernhardssonC, LarssonJ (2007) Painting of fourth and chromosome-wide regulation of the 4th chromosome in Drosophila melanogaster. EMBO J 26: 2307–2316.

81. JohanssonAM, StenbergP, PetterssonF, LarssonJ (2007) POF and HP1 bind expressed exons, suggesting a balancing mechanism for gene regulation. PLoS Genet 3: e209.

82. LarssonJ, ChenJD, RashevaV, Rasmuson LestanderA, PirrottaV (2001) Painting of fourth, a chromosome-specific protein in Drosophila. Proc Natl Acad Sci U S A 98: 6273–6278.

83. LyonMF (1998) X-chromosome inactivation: a repeat hypothesis. Cytogenet Cell Genet 80: 133–137.

84. CoelhoPA, Queiroz-MachadoJ, HartlD, SunkelCE (1998) Pattern of chromosomal localization of the Hoppel transposable element family in the Drosophila melanogaster subgroup. Chromosome Res 6: 385–395.

85. EllisonCE, BachtrogD (2013) Dosage compensation via transposable element mediated rewiring of a regulatory network. Science 342: 846–850.

86. ReaS, XouriG, AkhtarA (2007) Males absent on the first (MOF): from flies to humans. Oncogene 26: 5385–5394.

87. LiX, WuL, CorsaCA, KunkelS, DouY (2009) Two mammalian MOF complexes regulate transcription activation by distinct mechanisms. Mol Cell 36: 290–301.

88. AvnerP, HeardE (2001) X-chromosome inactivation: counting, choice and initiation. Nat Rev Genet 2: 59–67.

89. DorerDR, HenikoffS (1997) Transgene repeat arrays interact with distant heterochromatin and cause silencing in cis and trans. Genetics 147: 1181–1190.

90. de VanssayA, BougéAL, BoivinA, HermantC, TeyssetL, et al. (2012) Paramutation in Drosophila linked to emergence of a piRNA-producing locus. Nature 490: 112–115.

91. GrothAC, OlivaresEC, ThyagarajanB, CalosMP (2000) A phage integrase directs efficient site-specific integration in human cells. Proc Natl Acad Sci U S A 97: 5995–6000.

92. LundbergLE, KimM, JohanssonAM, FaucillionML, JosupeitR, et al. (2013) Targeting of Painting of fourth to roX1 and roX2 proximal sites suggests evolutionary links between dosage compensation and the regulation of the fourth chromosome in Drosophila melanogaster. G3 (Bethesda) 3: 1325–1334.

93. Sullivan W, Ashburner M, Hawley RS (2000) Drosophila protocols. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press.

94. JohanssonAM, StenbergP, AllgardssonA, LarssonJ (2012) POF regulates the expression of genes on the fourth chromosome in Drosophila melanogaster by binding to nascent RNA. Mol Cell Biol 32: 2121–2134.

95. LavrovS, DéjardinJ, CavalliG (2004) Combined immunostaining and FISH analysis of polytene chromosomes. Methods Mol Biol 247: 289–303.

96. HolmqvistPH, BoijaA, PhilipP, CronaF, StenbergP, et al. (2012) Preferential genome targeting of the CBP co-activator by Rel and Smad proteins in early Drosophila melanogaster embryos. PLoS Genet 8: e1002769.

97. BaileyTL, ElkanC (1994) Fitting a mixture model by expectation maximization to discover motifs in biopolymers. Proc Int Conf Intell Syst Mol Biol 2: 28–36.

98. AdamsMD, CelnikerSE, HoltRA, EvansCA, GocayneJD, et al. (2000) The genome sequence of Drosophila melanogaster. Science 287: 2185–2195.

99. CelnikerSE, WheelerDA, KronmillerB, CarlsonJW, HalpernA, et al. (2002) Finishing a whole-genome shotgun: release 3 of the Drosophila melanogaster euchromatic genome sequence. Genome Biol 3: RESEARCH0079.

100. JurkaJ, KapitonovVV, PavlicekA, KlonowskiP, KohanyO, et al. (2005) Repbase Update, a database of eukaryotic repetitive elements. Cytogenet Genome Res 110: 462–467.

101. LangmeadB, TrapnellC, PopM, SalzbergSL (2009) Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol 10: R25.

102. MortazaviA, WilliamsBA, McCueK, SchaefferL, WoldB (2008) Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nat Methods 5: 621–628.