Chromosoma

, Volume 119, Issue 1, pp 41–58 | Cite as

Synaptonemal complex stability depends on repressive histone marks of the lateral element-associated repeat sequences

  • Abrahan Hernández-Hernández
  • Rosario Ortiz
  • Ernestina Ubaldo
  • Olga M. Echeverría Martínez
  • Gerardo H. Vázquez-Nin
  • Félix Recillas-Targa
Research Article

Abstract

The synaptonemal complex (SC) is the central key structure for meiosis in organisms undergoing sexual reproduction. During meiotic prophase I, homologous chromosomes exchange genetic information at the time they are attached to the lateral elements by specific DNA sequences. Most of these sequences, so far identified, consist of repeat DNA, which are subject to chromatin structural changes during meiotic prophase I. In this work, we addressed the effect of altering the chromatin structure of repeat DNA sequences mediating anchorage to the lateral elements of the SC. Administration of the histone deacetylase inhibitor trichostatin A into live rats caused death of cells in the pachytene stage as well as changes in histone marks along the synaptonemal complex. The most notable effect was partial loss of histone H3 lysine 27 trimethylation. Our work describes the epigenetic landscape of lateral element-associated chromatin and reveals a critical role of histone marks in synaptonemal complex integrity.

Keywords

HDAC Inhibition Seminiferous Tubule Synaptonemal Complex Histone Mark Meiotic Prophase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

We thank Sidney Carter, Catherine M. Farrell, and Paul Delgado-Olguín for critical reading of the manuscript and suggestions. We would like to thank members of our research group for stimulating scientific discussions and suggestions. AHH is a fellowship recipient from the Posgrado en Ciencias Biológicas, CONACyT (181375). This work was supported by grants from the Dirección General de Asuntos del Personal Académico—UNAM (IN209403 and IN214407) and Consejo Nacional de Ciencia y Tecnología-CONACyT (42653-Q and 58767) to FRT. CONACyT (81213), DGAPA-PAPIIT (IN203308-3) to GHVN. We also acknowledge the excellent technical assistance of Georgina Guerrero Avendaño.

Supplementary material

412_2009_243_Fig15_ESM.jpg (350 kb)
Fig. S1

Experimental strategy for TSA administration in rats. The epithelium seminiferous cycle of the rat takes 29.5 days (29.5d). TSA daily administration started at the preleptotene stage (10.5d), when axial element formation starts, and was continued until 19d, corresponding to the pachytene stage. Rats at 2 months (2mt) after birth (0 dab) were divided into three groups (A, B, and C) of two animals each. Rats in group A were treated with 2.4 mg/kg of TSA, whereas rats in group B were injected only with dilution vehicle, and rats in group C were not treated. Meiotic division I and II finished at day 29.5 (MI and MII). After treatment, rats were sacrificed, and their testes were excised and split to perform the histochemistry, immunohistochemistry, electron microscopy analyses, and chromatin immunoprecipitation assays. (JPEG 350 kb)

412_2009_243_Fig16_ESM.jpg (648 kb)
Fig. S2

TUNEL assay. AF Seminiferous tubules of control rats stained with DAPI, B TUNEL assay and C phase-contrast image. D Seminiferous tubules of TSA-treated rats stained with DAPI, E TUNEL assay and F phase-contrast image. The TUNEL assay in E shows more cellular death as compared with the control seminiferous tubule in B. The bar represents 50 μm. GL Hematoxylin–eosin staining of gonad sections showing cells in different stages of the CSE. G–I Sections of control rats in stages III, IX, and XII of the CSE. J–L Sections of TSA-treated rats in stages III, IX, and XII of the CSE. eP early pachytene; mP mid pachytene; Di diplotene; Z zygotene; 3, 9, 13, and 16 stages of spermiogenesis. Asterisks in K indicate remaining early pachytene cells. The bar corresponds to 10 μm (JPEG 648 kb)

References

  1. Adler ID (1996) Comparison of the duration of spermatogenesis between male rodents and humans. Mutat Res 352:169–172PubMedGoogle Scholar
  2. Barski A, Cuddapah S, Cui K, Roh TY, Schones DE, Wang Z, Wei G, Chepelev I, Zhao K (2007) High-resolution profiling of histone methylations in the human genome. Cell 129:823–837CrossRefPubMedGoogle Scholar
  3. Benetti R, García-Cao M, Blasco MA (2007) Telomere length regulates the epigenetic status of mammalian telomeres and subtelomeres. Nat Genet 39:243–250CrossRefPubMedGoogle Scholar
  4. Bolcun-Filas E, Costa Y, Speed R, Taggart M, Benavente R, De Rooij DG, Cooke HJ (2007) SYCE2 is required for synaptonemal complex assembly, double strand break repair, and homologous recombination. J Cell Biol 176:741–747CrossRefPubMedGoogle Scholar
  5. Borde V, Robine N, Lin W, Bonfils S, Géli V, Nicolas A (2009) Histone H3 lysine 4 trimethylation marks meiotic recombination initiation sites. EMBO J 28:99–111CrossRefPubMedGoogle Scholar
  6. Clermont Y (1972) Kinetics of spermatogenesis in mammals: seminiferous epithelium cycle and spermatogonial renewal. Physiol Rev 52:198–236PubMedGoogle Scholar
  7. Cogliati R, Gautier A (1973) Mise en évidence de l’ADN et des polysaccharides á l’aide d’un nouveau réactif de type Schiff. C R Acad Sci D 276:3041–3044Google Scholar
  8. Godmann M, Auger V, Ferraroni-Aguiar V, Di Sauro A, Sette C, Behr R, Kimmins S (2007) Dynamic regulation of histone H3 methylation at lysine 4 in mammalian spermatogenesis. Biol Reprod 77:754–764CrossRefPubMedGoogle Scholar
  9. Ekwall K, Olsson T, Turner BM, Cranston G, Allshire RC (1997) Transient inhibition of histone deacetylation alters the structural and functional imprint at fission yeast centromeres. Cell 91:1021–1032CrossRefPubMedGoogle Scholar
  10. Fenic I, Hossain HM, Sonnack V, Tchatalbachev S, Thierer F, Trapp J, Failing K, Edler KS, Bergmann M, Jung M, Chakraborty T, Steger K (2008) In vivo application of histone deacetylase inhibitor trichostatin-A impairs murine male meiosis. J Androl 29:172–185CrossRefPubMedGoogle Scholar
  11. Fenic I, Sonnack V, Failing K, Bergmann M, Steger K (2004) In vivo effects of histone-deacetylase inhibitor trichostatin-A on murine spermatogenesis. J Androl 25:811–818PubMedGoogle Scholar
  12. National Research Council (NRC) (1996) Guide for the care and use of laboratory animals. The National Academy Press, Washington DCGoogle Scholar
  13. Hernández-Hernández A, Rincón-Arano H, Recillas-Targa F, Ortiz R, Valdes-Quezada C, Echeverría OM, Benavente R, Vázquez-Nin GH (2008) Differential distribution and association of repeat DNA sequences in the lateral element of the synaptonemal complex in rat spermatocytes. Chromosoma 117:77–87CrossRefPubMedGoogle Scholar
  14. Hernández-Hernández A, Vázquez-Nin GH, Echeverría OM, Recillas-Targa F (2009) Chromatin structure contribution to the synaptonemal complex formation. Cell Mol Life Sci 66:1198–1208CrossRefPubMedGoogle Scholar
  15. Khalil AM, Boyar FZ, Driscoll DJ (2004) Dynamic histone modifications mark sex chromosome inactivation and reactivation during mammalian spermatogenesis. Proc Natl Acad Sci USA 101:16583–16587CrossRefPubMedGoogle Scholar
  16. Martens JHA, O’Sullivan RJ, Braunschweig U, Opravil S, Radolf M, Steinlein P, Jenuwein T (2005) The profile of repeat-associated histone lysine methylation states in the mouse epigenome. EMBO J 24:800–812CrossRefPubMedGoogle Scholar
  17. Merker JD, Dominska M, Greenwell PW, Rinella E, Bouck DC, Shibata Y, Strahl BD, Mieczkowski P, Petes TD (2008) The histone methylase Set2p and the histone deacetylase Rpd3p repress meiotic recombination at the HIS4 meiotic recombination hotspot in Saccharomyces cerevisiae. DNA Repair 7:1298–1308CrossRefPubMedGoogle Scholar
  18. Ortíz R, Echeverría OM, Ubaldo E, Carlos A, Scassellati C, Vázquez-Nin GH (2002) Cytochemical study of the distribution of the RNA and DNA in the synaptonemal complex of guinea-pig and rat spermatocytes. Eur J Histochem 46:133–142PubMedGoogle Scholar
  19. Page SL, Hawley RS (2004) The genetics and molecular biology of the synaptonemal complex. Annu Rev Cell Dev Biol 20:525–558CrossRefPubMedGoogle Scholar
  20. Peters AH, O’Carroll D, Schertan H, Mechtler K, Sauer S, Schöfer C, Weipoltshammer K, Pagani M, Lachner M, Kohlmaier A, Opravil S, Doyle M, Sibilia M, Jenuwein T (2001) Loss of the Suv39h histone methyltransferases impairs mammalian heterochromatin and genome stability. Cell 117:323–337CrossRefGoogle Scholar
  21. Prieto I, Kouznetsova A, Fütterer A, Trachana V, Leonardo E, Alonso Guerrero A, Cano Gamero M, Pacios-Bras C, Leh H, Buckle M, Garcia-Gallo M, Kremer L, Serrano A, Roncal F, Albar JP, Barbero JL, Martínez-A C, van Wely KH (2009) Synaptonemal complex assembly and H3K4Me3 demethylation determine DIDO3 localization in meiosis. Chromosoma 118:617–632CrossRefPubMedGoogle Scholar
  22. Rincón-Arano H, Furlan-Magaril M, Recillas-Targa F (2007) Protection against telomeric position effects by the chicken cHS4 β-globin insulator. Proc Natl Acad Sci USA 104:14044–14049CrossRefPubMedGoogle Scholar
  23. Tachibana M, Nozaki M, Takeda N, Shinkai Y (2007) Functional dynamics of H3K9 methylation during meiotic prophase progression. EMBO J 26:3346–3359CrossRefPubMedGoogle Scholar
  24. Vallente RU, Cheng EY, Hassold TJ (2006) The synaptonemal complex and meiotic recombination in humans: new approaches to old questions. Chromosoma 115:241–249CrossRefPubMedGoogle Scholar
  25. Viera A, Parra MT, Page J, Santos JL, Rufas JS, Suja JA (2003) Dynamic relocation of telomere complexes in mouse meiotic chromosomes. Chromosome Res 11:797–807CrossRefPubMedGoogle Scholar
  26. Yamashita K, Shinohara M, Shinohara A (2004) Rad6-Bre1-mediated histone H2B ubiquitylation modulates the formation of double-strand breaks during meiosis. Proc Natl Acad Sci USA 101:11380–11385CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Abrahan Hernández-Hernández
    • 1
    • 2
  • Rosario Ortiz
    • 1
  • Ernestina Ubaldo
    • 1
  • Olga M. Echeverría Martínez
    • 1
  • Gerardo H. Vázquez-Nin
    • 1
  • Félix Recillas-Targa
    • 2
  1. 1.Laboratorio de Microscopía Electrónica, Departamento de Biología Celular, Facultad de CienciasUniversidad Nacional Autónoma de México (UNAM)México D.F.Mexico
  2. 2.Instituto de Fisiología Celular, Departamento de Genética MolecularUniversidad Nacional Autónoma de México (UNAM)México D.F.Mexico

Personalised recommendations