Meiotic Cohesin SMC1β Provides Prophase I Centromeric Cohesion and Is Required for Multiple Synapsis-Associated Functions
Cohesin subunit SMC1β is specific and essential for meiosis. Previous studies showed functions of SMC1β in determining the axis-loop structure of synaptonemal complexes (SCs), in providing sister chromatid cohesion (SCC) in metaphase I and thereafter, in protecting telomere structure, and in synapsis. However, several central questions remained unanswered and concern roles of SMC1β in SCC and synapsis and processes related to these two processes. Here we show that SMC1β substantially supports prophase I SCC at centromeres but not along chromosome arms. Arm cohesion and some of centromeric cohesion in prophase I are provided by non-phosphorylated SMC1α. Besides supporting synapsis of autosomes, SMC1β is also required for synapsis and silencing of sex chromosomes. In absence of SMC1β, the silencing factor γH2AX remains associated with asynapsed autosomes and fails to localize to sex chromosomes. Microarray expression studies revealed up-regulated sex chromosome genes and many down-regulated autosomal genes. SMC1β is further required for non-homologous chromosome associations observed in absence of SPO11 and thus of programmed double-strand breaks. These breaks are properly generated in Smc1β−/− spermatocytes, but their repair is delayed on asynapsed chromosomes. SMC1α alone cannot support non-homologous associations. Together with previous knowledge, three main functions of SMC1β have emerged, which have multiple consequences for spermatocyte biology: generation of the loop-axis architecture of SCs, homologous and non-homologous synapsis, and SCC starting in early prophase I.
Vyšlo v časopise:
Meiotic Cohesin SMC1β Provides Prophase I Centromeric Cohesion and Is Required for Multiple Synapsis-Associated Functions. PLoS Genet 9(12): e32767. doi:10.1371/journal.pgen.1003985
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1003985
Souhrn
Cohesin subunit SMC1β is specific and essential for meiosis. Previous studies showed functions of SMC1β in determining the axis-loop structure of synaptonemal complexes (SCs), in providing sister chromatid cohesion (SCC) in metaphase I and thereafter, in protecting telomere structure, and in synapsis. However, several central questions remained unanswered and concern roles of SMC1β in SCC and synapsis and processes related to these two processes. Here we show that SMC1β substantially supports prophase I SCC at centromeres but not along chromosome arms. Arm cohesion and some of centromeric cohesion in prophase I are provided by non-phosphorylated SMC1α. Besides supporting synapsis of autosomes, SMC1β is also required for synapsis and silencing of sex chromosomes. In absence of SMC1β, the silencing factor γH2AX remains associated with asynapsed autosomes and fails to localize to sex chromosomes. Microarray expression studies revealed up-regulated sex chromosome genes and many down-regulated autosomal genes. SMC1β is further required for non-homologous chromosome associations observed in absence of SPO11 and thus of programmed double-strand breaks. These breaks are properly generated in Smc1β−/− spermatocytes, but their repair is delayed on asynapsed chromosomes. SMC1α alone cannot support non-homologous associations. Together with previous knowledge, three main functions of SMC1β have emerged, which have multiple consequences for spermatocyte biology: generation of the loop-axis architecture of SCs, homologous and non-homologous synapsis, and SCC starting in early prophase I.
Zdroje
1. KlecknerN (2006) Chiasma formation: chromatin/axis interplay and the role(s) of the synaptonemal complex. Chromosoma 115: 175–194.
2. CostaY, CookeH (2007) Dissecting the mammalian synaptonemal complex using targeted mutations. Chromosome Research 15: 579.
3. HandelMA, SchimentiJC (2010) Genetics of mammalian meiosis: regulation, dynamics and impact on fertility. Nat Rev Genet 11: 124–136.
4. LichtenM, de MassyB (2011) The impressionistic landscape of meiotic recombination. Cell 147: 267–270.
5. YoudsJL, BoultonSJ (2011) The choice in meiosis - defining the factors that influence crossover or non-crossover formation. J Cell Sci 124: 501–513.
6. SasakiM, LangeJ, KeeneyS (2010) Genome destabilization by homologous recombination in the germ line. Nat Rev Mol Cell Biol 11: 182–195.
7. KeeneyS (2008) Spo11 and the Formation of DNA Double-Strand Breaks in Meiosis. Genome Dyn Stab 2: 81–123.
8. YanowitzJ (2010) Meiosis: making a break for it. Curr Opin Cell Biol 22: 744–751.
9. BurgoynePS, MahadevaiahSK, TurnerJM (2009) The consequences of asynapsis for mammalian meiosis. Nat Rev Genet 10: 207–216.
10. FukudaT, DanielK, WojtaszL, TothA, HoogC (2010) A novel mammalian HORMA domain-containing protein, HORMAD1, preferentially associates with unsynapsed meiotic chromosomes. Exp Cell Res 316: 158–171.
11. WojtaszL, DanielK, RoigI, Bolcun-FilasE, XuH, et al. (2009) Mouse HORMAD1 and HORMAD2, two conserved meiotic chromosomal proteins, are depleted from synapsed chromosome axes with the help of TRIP13 AAA-ATPase. PLoS Genet 5: e1000702.
12. RomanienkoPJ, Camerini-OteroRD (2000) The mouse Spo11 gene is required for meiotic chromosome synapsis. Mol Cell 6: 975–987.
13. BaudatF, ManovaK, YuenJP, JasinM, KeeneyS (2000) Chromosome synapsis defects and sexually dimorphic meiotic progression in mice lacking Spo11. Mol Cell 6: 989–998.
14. EllisN, GoodfellowPN (1989) The mammalian pseudoautosomal region. Trends Genet 5: 406–410.
15. PerryJ, PalmerS, GabrielA, AshworthA (2001) A short pseudoautosomal region in laboratory mice. Genome Res 11: 1826–1832.
16. AndersonLK, ReevesA, WebbLM, AshleyT (1999) Distribution of crossing over on mouse synaptonemal complexes using immunofluorescent localization of MLH1 protein. Genetics 151: 1569–1579.
17. KauppiL, BarchiM, BaudatF, RomanienkoPJ, KeeneyS, et al. (2011) Distinct properties of the XY pseudoautosomal region crucial for male meiosis. Science 331: 916–920.
18. InagakiA, SchoenmakersS, BaarendsWM (2010) DNA double strand break repair, chromosome synapsis and transcriptional silencing in meiosis. Epigenetics 5: 255–266.
19. YanW, McCarreyJR (2009) Sex chromosome inactivation in the male. Epigenetics 4: 452–456.
20. HandelMA (2004) The XY body: a specialized meiotic chromatin domain. Exp Cell Res 296: 57–63.
21. Fernandez-CapetilloO, MahadevaiahSK, CelesteA, RomanienkoPJ, Camerini-OteroRD, et al. (2003) H2AX is required for chromatin remodeling and inactivation of sex chromosomes in male mouse meiosis. Dev Cell 4: 497–508.
22. PageJ, de la FuenteR, ManterolaM, ParraMT, VieraA, et al. (2012) Inactivation or non-reactivation: what accounts better for the silence of sex chromosomes during mammalian male meiosis? Chromosoma 121: 307–326.
23. TurnerJM, MahadevaiahSK, Fernandez-CapetilloO, NussenzweigA, XuX, et al. (2005) Silencing of unsynapsed meiotic chromosomes in the mouse. Nat Genet 37: 41–47.
24. MahadevaiahSK, Bourc'hisD, de RooijDG, BestorTH, TurnerJM, et al. (2008) Extensive meiotic asynapsis in mice antagonises meiotic silencing of unsynapsed chromatin and consequently disrupts meiotic sex chromosome inactivation. J Cell Biol 182: 263–276.
25. TurnerJM (2007) Meiotic sex chromosome inactivation. Development 134: 1823–1831.
26. RoyoH, PolikiewiczG, MahadevaiahSK, ProsserH, MitchellM, et al. (2010) Evidence that meiotic sex chromosome inactivation is essential for male fertility. Curr Biol 20: 2117–2123.
27. NasmythK, HaeringCH (2009) Cohesin: its roles and mechanisms. Annu Rev Genet 43: 525–558.
28. ShintomiK, HiranoT (2010) Sister chromatid resolution: a cohesin releasing network and beyond. Chromosoma 119: 459–467.
29. OnnI, Heidinger-PauliJM, GuacciV, UnalE, KoshlandDE (2008) Sister chromatid cohesion: a simple concept with a complex reality. Annu Rev Cell Dev Biol 24: 105–129.
30. WoodAJ, SeversonAF, MeyerBJ (2010) Condensin and cohesin complexity: the expanding repertoire of functions. Nat Rev Genet 11: 391–404.
31. NasmythK (2011) Cohesin: a catenase with separate entry and exit gates? Nat Cell Biol 13: 1170–1177.
32. HaeringCH, JessbergerR (2012) Cohesin in determining chromosome architecture. Exp Cell Res 318: 1386–1393.
33. UhlmannF (2011) Cohesin subunit Rad21L, the new kid on the block has new ideas. EMBO Rep 12: 183–184.
34. JessbergerR (2011) Cohesin complexes get more complex: the novel kleisin RAD21L. Cell Cycle 10: 2053–2054.
35. RevenkovaE, EijpeM, HeytingC, GrossB, JessbergerR (2001) Novel meiosis-specific isoform of mammalian SMC1. Mol Cell Biol 21: 6984–6998.
36. RevenkovaE, EijpeM, HeytingC, HodgesCA, HuntPA, et al. (2004) Cohesin SMC1 beta is required for meiotic chromosome dynamics, sister chromatid cohesion and DNA recombination. Nat Cell Biol 6: 555–562.
37. HodgesCA, RevenkovaE, JessbergerR, HassoldTJ, HuntPA (2005) SMC1beta-deficient female mice provide evidence that cohesins are a missing link in age-related nondisjunction. Nat Genet 37: 1351–1355.
38. StromL, SjogrenC (2007) Chromosome segregation and double-strand break repair - a complex connection. Curr Opin Cell Biol 19: 344–349.
39. WatrinE, PetersJM (2006) Cohesin and DNA damage repair. Exp Cell Res 312: 2687–2693.
40. FeeneyKM, WassonCW, ParishJL (2010) Cohesin: a regulator of genome integrity and gene expression. Biochem J 428: 147–161.
41. Cortes-LedesmaF, de PiccoliG, HaberJE, AragonL, AguileraA (2007) SMC proteins, new players in the maintenance of genomic stability. Cell Cycle 6: 914–918.
42. WendtKS, PetersJM (2009) How cohesin and CTCF cooperate in regulating gene expression. Chromosome Res 17: 201–214.
43. MerkenschlagerM (2010) Cohesin: a global player in chromosome biology with local ties to gene regulation. Curr Opin Genet Dev 20: 555–561.
44. DorsettD (2011) Cohesin: genomic insights into controlling gene transcription and development. Curr Opin Genet Dev 21: 199–206.
45. BoseT, GertonJL (2010) Cohesinopathies, gene expression, and chromatin organization. J Cell Biol 189: 201–210.
46. AdelfalkC, JanschekJ, RevenkovaE, BleiC, LiebeB, et al. (2009) Cohesin SMC1beta protects telomeres in meiocytes. J Cell Biol 187: 185–199.
47. ScherthanH, JerratschM, LiB, SmithS, HultenM, et al. (2000) Mammalian meiotic telomeres: protein composition and redistribution in relation to nuclear pores. Mol Biol Cell 11: 4189–4203.
48. PetersAH, PlugAW, van VugtMJ, de BoerP (1997) A drying-down technique for the spreading of mammalian meiocytes from the male and female germline. Chromosome Res 5: 66–68.
49. LeeJ, HiranoT (2011) RAD21L, a novel cohesin subunit implicated in linking homologous chromosomes in mammalian meiosis. J Cell Biol 192: 263–276.
50. EijpeM, HeytingC, GrossB, JessbergerR (2000) Association of mammalian SMC1 and SMC3 proteins with meiotic chromosomes and synaptonemal complexes. J Cell Sci 113(Pt 4): 673–682.
51. TakadaY, NaruseC, CostaY, ShirakawaT, TachibanaM, et al. (2011) HP1gamma links histone methylation marks to meiotic synapsis in mice. Development 138: 4207–4217.
52. BaumannC, DalyCM, McDonnellSM, ViveirosMM, De La FuenteR (2011) Chromatin configuration and epigenetic landscape at the sex chromosome bivalent during equine spermatogenesis. Chromosoma 120: 227–244.
53. LangeJ, PanJ, ColeF, ThelenMP, JasinM, et al. (2011) ATM controls meiotic double-strand-break formation. Nature 479: 237–240.
54. RozenS, SkaletskyH (2000) Primer3 on the WWW for general users and for biologist programmers. Methods Mol Biol 132: 365–386.
55. WilcoxonF (1945) Individual comparisons by ranking methods. Biometrics Bulletin 1: 80–83.
56. SeifertM, StrickertM, SchliepA, GrosseI (2011) Exploiting prior knowledge and gene distances in the analysis of tumor expression profiles with extended Hidden Markov Models. Bioinformatics 27: 1645–1652.
57. NovakI, WangH, RevenkovaE, JessbergerR, ScherthanH, et al. (2008) Cohesin Smc1beta determines meiotic chromatin axis loop organization. J Cell Biol 180: 83–90.
58. de CarvalhoCE, ColaiacovoMP (2006) SUMO-mediated regulation of synaptonemal complex formation during meiosis. Genes Dev 20: 1986–1992.
59. RogersRS, InselmanA, HandelMA, MatunisMJ (2004) SUMO modified proteins localize to the XY body of pachytene spermatocytes. Chromosoma 113: 233–243.
60. VigodnerM, MorrisPL (2005) Testicular expression of small ubiquitin-related modifier-1 (SUMO-1) supports multiple roles in spermatogenesis: silencing of sex chromosomes in spermatocytes, spermatid microtubule nucleation, and nuclear reshaping. Dev Biol 282: 480–492.
61. FukudaT, PrattoF, SchimentiJC, TurnerJM, Camerini-OteroRD, et al. (2012) Phosphorylation of Chromosome Core Components May Serve as Axis Marks for the Status of Chromosomal Events during Mammalian Meiosis. PLoS Genet 8: e1002485.
62. YazdiPT, WangY, ZhaoS, PatelN, LeeEY, et al. (2002) SMC1 is a downstream effector in the ATM/NBS1 branch of the human S-phase checkpoint. Genes Dev 16: 571–582.
63. KimST, XuB, KastanMB (2002) Involvement of the cohesin protein, Smc1, in Atm-dependent and independent responses to DNA damage. Genes Dev 16: 560–570.
64. LiefshitzB, KupiecM (2011) Roles of RSC, Rad59, and cohesin in double-strand break repair. Mol Cell Biol 31: 3921–3923.
65. Heidinger-PauliJM, UnalE, GuacciV, KoshlandD (2008) The kleisin subunit of cohesin dictates damage-induced cohesion. Mol Cell 31: 47–56.
66. JamesRD, SchmiesingJA, PetersAH, YokomoriK, DistecheCM (2002) Differential association of SMC1alpha and SMC3 proteins with meiotic chromosomes in wild-type and SPO11-deficient male mice. Chromosome Res 10: 549–560.
67. NealeMJ, PanJ, KeeneyS (2005) Endonucleolytic processing of covalent protein-linked DNA double-strand breaks. Nature 436: 1053–1057.
68. BellaniMA, BoatengKA, McLeodD, Camerini-OteroRD (2010) The expression profile of the major mouse SPO11 isoforms indicates that SPO11beta introduces double strand breaks and suggests that SPO11alpha has an additional role in prophase in both spermatocytes and oocytes. Mol Cell Biol 30: 4391–4403.
69. ColeF, KauppiL, LangeJ, RoigI, WangR, et al. (2012) Homeostatic control of recombination is implemented progressively in mouse meiosis. Nat Cell Biol 14: 424–430.
70. MurdochB, OwenN, StevenseM, SmithH, NagaokaS, et al. (2013) Altered cohesin gene dosage affects Mammalian meiotic chromosome structure and behavior. PLoS Genet 9: e1003241.
71. EijpeM, OffenbergH, JessbergerR, RevenkovaE, HeytingC (2003) Meiotic cohesin REC8 marks the axial elements of rat synaptonemal complexes before cohesins SMC1beta and SMC3. J Cell Biol 160: 657–670.
72. TothA, JessbergerR (2010) Male meiosis: Y keep it silenced? Curr Biol 20: R1022–1024.
73. BellaniMA, RomanienkoPJ, CairattiDA, Camerini-OteroRD (2005) SPO11 is required for sex-body formation, and Spo11 heterozygosity rescues the prophase arrest of Atm-/- spermatocytes. J Cell Sci 118: 3233–3245.
74. BarchiM, RoigI, Di GiacomoM, de RooijDG, KeeneyS, et al. (2008) ATM promotes the obligate XY crossover and both crossover control and chromosome axis integrity on autosomes. PLoS Genet 4: e1000076.
75. AlmstrupK, NielsenJE, HansenMA, TanakaM, SkakkebaekNE, et al. (2004) Analysis of cell-type-specific gene expression during mouse spermatogenesis. Biol Reprod 70: 1751–1761.
76. RossiP, DolciS, SetteC, CapolunghiF, PellegriniM, et al. (2004) Analysis of the gene expression profile of mouse male meiotic germ cells. Gene Expr Patterns 4: 267–281.
77. ChalmelF, RollandAD, Niederhauser-WiederkehrC, ChungSS, DemouginP, et al. (2007) The conserved transcriptome in human and rodent male gametogenesis. Proc Natl Acad Sci U S A 104: 8346–8351.
78. PangAL, JohnsonW, RavindranathN, DymM, RennertOM, et al. (2006) Expression profiling of purified male germ cells: stage-specific expression patterns related to meiosis and postmeiotic development. Physiol Genomics 24: 75–85.
79. SmirnovaNA, RomanienkoPJ, KhilPP, Camerini-OteroRD (2006) Gene expression profiles of Spo11-/- mouse testes with spermatocytes arrested in meiotic prophase I. Reproduction 132: 67–77.
80. BastosH, LassalleB, ChicheporticheA, RiouL, TestartJ, et al. (2005) Flow cytometric characterization of viable meiotic and postmeiotic cells by Hoechst 33342 in mouse spermatogenesis. Cytometry A 65: 40–49.
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
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