Skip to main content
Log in

SUMO modified proteins localize to the XY body of pachytene spermatocytes

  • Research Article
  • Published:
Chromosoma Aims and scope Submit manuscript

Abstract

The XY body is a specialized chromatin territory that forms during meiotic prophase of spermatogenesis and comprises the transcriptionally repressed sex chromosomes. Remodeling of the XY chromatin is brought about by recruitment of specific proteins to the X and Y chromosomes during meiosis, and also by post-translational modifications of histones and other chromatin-associated proteins. Here, we demonstrate that SUMO, a small ubiquitin-related modifier protein that regulates a wide variety of nuclear functions in somatic cells, dramatically localizes to the XY body. SUMO was first detected in the XY body of early pachytene spermatocytes and gradually accumulated, reaching maximal levels there during the mid to late pachytene stages. Several known SUMO substrates, including PML and DAXX, were also found to accumulate in the XY body of mid to late stage pachytene spermatocytes. These same proteins localize to PML nuclear bodies of somatic interphase nuclei. Together, these findings indicate a role for SUMO modification in regulating the structure and function of the XY body and reveal molecular similarities between the XY body and PML nuclear bodies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1a, b
Fig. 2a, b
Fig. 3a–c
Fig. 4a–d
Fig. 5a–f
Fig. 6
Fig. 7a–f
Fig. 8a–h

Similar content being viewed by others

References

  • Apionishev S, Malhotra D, Raghavachari S, Tanda S, Rasooly RS (2001) The Drosophila UBC9 homologue lesswright mediates the disjunction of homologues in meiosis, I. Genes Cells 6:215–224

    Article  CAS  PubMed  Google Scholar 

  • Azuma Y, Arnaoutov A, Dasso M (2003) SUMO-2/3 regulates topoisomerase II in mitosis. J Cell Biol 163:477–487

    Article  CAS  PubMed  Google Scholar 

  • Bachant J, Alcasabas A, Blat Y, Kleckner N, Elledge SJ (2002) The SUMO-1 isopeptidase Smt4 is linked to centromeric cohesion through SUMO-1 modification of DNA topoisomerase, II. Mol Cell 9:1169–1182

    Article  CAS  PubMed  Google Scholar 

  • Biggins S, Bhalla N, Chang A, Smith DL, Murray AW (2001) Genes involved in sister chromatid separation and segregation in the budding yeast Saccharomyces cerevisiae. Genetics 159:453–470

    CAS  PubMed  Google Scholar 

  • van Brabant AJ, Stan R, Ellis NA (2000) DNA helicases, genomic instability, and human genetic disease. Annu Rev Genomics Hum Genet 1:409–459

    Article  PubMed  Google Scholar 

  • Cobb J, Handel MA (1998) Dynamics of meiotic prophase I during spermatogenesis: from pairing to division. Semin Cell Dev Biol 9:445–450

    Article  CAS  PubMed  Google Scholar 

  • Cobb J, Cargile B, Handel MA (1999) Acquisition of competence to condense metaphase I chromosomes during spermatogenesis. Dev Biol 205:49–64

    Article  CAS  PubMed  Google Scholar 

  • Cohen PE, Pollard JW (2001) Regulation of meiotic recombination and prophase I progression in mammals. Bioessays 23:996–1009

    Article  CAS  PubMed  Google Scholar 

  • Eaker S, Pyle A, Cobb J, Handel MA (2001) Evidence for meiotic spindle checkpoint from analysis of spermatocytes from Robertsonian-chromosome heterozygous mice. J Cell Sci 114:2953–2965

    CAS  PubMed  Google Scholar 

  • Eijpe M, Offenberg H, Goedecke W, Heyting C (2000) Localisation of RAD50 and MRE11 in spermatocyte nuclei of mouse and rat. Chromosoma 109:123–132

    Article  CAS  PubMed  Google Scholar 

  • Fernandez-Capetillo O, Mahadevaiah SK, Celeste A, Romanienko PJ, Camerini-Otero RD, Bonner WM, Manova K, Burgoyne P, Nussenzweig A (2003) H2AX is required for chromatin remodeling and inactivation of sex chromosomes in male mouse meiosis. Dev Cell 4:497–508

    Article  CAS  PubMed  Google Scholar 

  • Girdwood D, Bumpass D, Vaughan OA, Thain A, Anderson LA, Snowden AW, Garcia-Wilson E, Perkins ND, Hay RT (2003) P300 transcriptional repression is mediated by SUMO modification. Mol Cell 11:1043–1054

    Article  CAS  PubMed  Google Scholar 

  • Gostissa M, Hengstermann A, Fogal V, Sandy P, Schwarz SE, Scheffner M, Del Sal G (1999) Activation of p53 by conjugation to the ubiquitin-like protein SUMO-1. EMBO J 18:6462–6471

    CAS  PubMed  Google Scholar 

  • Handel MA (2004) The XY body: a specialized meiotic chromatin domain. Exp Cell Res 296:57–63

    Article  CAS  PubMed  Google Scholar 

  • Hari KL, Cook KR, Karpen GH (2001) The Drosophila Su(var)2–10 locus regulates chromosome structure and function and encodes a member of the PIAS protein family. Genes Dev 15:1334–1348

    Article  CAS  PubMed  Google Scholar 

  • Hoege C, Pfander B, Moldovan GL, Pyrowolakis G, Jentsch S (2002) RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMO. Nature 419:135–141

    Article  CAS  Google Scholar 

  • Hoyer-Fender S (2003) Molecular aspects of XY body formation. Cytogenet Genome Res 103:245–255

    Article  CAS  PubMed  Google Scholar 

  • Inselman A, Eaker S, Handel MA (2003) Temporal expression of cell cycle-related proteins during spermatogenesis: establishing a timeline for onset of the meiotic divisions. Cytogenet Genome Res 103:277–284

    Article  CAS  PubMed  Google Scholar 

  • Ishov AM, Sotnikov AG, Negorev D, Vladimirova OV, Neff N, Kamitani T, Yeh ET, Strauss JF 3, Maul GG (1999) PML is critical for ND10 formation and recruits the PML-interacting protein daxx to this nuclear structure when modified by SUMO-1. J Cell Biol 147:221–234

    Article  CAS  PubMed  Google Scholar 

  • Jang MS, Ryu SW, Kim E (2002) Modification of Daxx by small ubiquitin-related modifier-1. Biochem Biophys Res Commun 295:495–500

    Google Scholar 

  • Kagey MH, Melhuish TA, Wotton D (2003) The polycomb protein Pc2 is a SUMO E3. Cell 113:127–137

    Article  CAS  PubMed  Google Scholar 

  • Kawabe Y, Seki M, Seki T, Wang WS, Imamura O, Furuichi Y, Saitoh H, Enomoto T (2000) Covalent modification of the Werner’s syndrome gene product with the ubiquitin-related protein, SUMO-1. J Biol Chem 275:20963–20966

    Article  CAS  PubMed  Google Scholar 

  • Kovalenko OV, Plug AW, Haaf T, Gonda DK, Ashley T, Ward DC, Radding CM, Golub EI (1996) Mammalian ubiquitin-conjugating enzyme Ubc9 interacts with Rad51 recombination protein and localizes in synaptonemal complexes. Proc Natl Acad Sci USA 93:2958–2963

    Article  CAS  PubMed  Google Scholar 

  • Kralewski M, Novello A, Benavente R (1997) A novel Mr 77,000 protein of the XY body of mammalian spermatocytes: its localization in normal animals and in Searle’s translocation carriers. Chromosoma 106:160–167

    Article  CAS  PubMed  Google Scholar 

  • Li SJ, Hochstrasser M (1999) A new protease required for cell-cycle progression in yeast. Nature 398:246–251

    Article  CAS  PubMed  Google Scholar 

  • Li H, Leo C, Zhu J, Wu X, O’Neil J, Park EJ, Chen JD (2000a) Sequestration and inhibition of Daxx-mediated transcriptional repression by PML. Mol Cell Biol 20:1784–1796

    Article  CAS  PubMed  Google Scholar 

  • Li W, Hesabi B, Babbo A, Pacione C, Liu J, Chen DJ, Nickoloff JA, Shen Z (2000b) Regulation of double-strand break-induced mammalian homologous recombination by UBL1, a RAD51-interacting protein. Nucleic Acids Res 28:1145–1153

    Article  CAS  PubMed  Google Scholar 

  • Lombard DB, Guarente L (2000) Nijmegen breakage syndrome disease protein and MRE11 at PML nuclear bodies and meiotic telomeres. Cancer Res 60:2331–2334

    CAS  PubMed  Google Scholar 

  • Mahadevaiah SK, Turner JM, Baudat F, Rogakou EP, de Boer P, Blanco-Rodriguez J, Jasin M, Keeney S, Bonner WM, Burgoyne PS (2001) Recombinational DNA double-strand breaks in mice precede synapsis. Nat Genet 27:271–276

    Article  CAS  PubMed  Google Scholar 

  • Mao Y, Desai SD, Liu LF (2000a) SUMO-1 conjugation to human DNA topoisomerase II isozymes. J Biol Chem 275:26066–26073

    Article  CAS  PubMed  Google Scholar 

  • Mao Y, Sun M, Desai SD, Liu LF (2000b) SUMO-1 conjugation to topoisomerase. I. A possible repair response to topoisomerase-mediated DNA damage. Proc Natl Acad Sci USA 97:4046–4051

    Article  CAS  PubMed  Google Scholar 

  • Matunis MJ, Coutavas E, Blobel G (1996) A novel ubiquitin-like modification modulates the partitioning of the Ran-GTPase-activating protein RanGAP1 between the cytosol and the nuclear pore complex. J Cell Biol 135:1457–1470

    Article  CAS  PubMed  Google Scholar 

  • Maul GG, Everett RD (1994) The nuclear location of PML, a cellular member of the C3HC4 zinc-binding domain protein family, is rearranged during herpes simplex virus infection by the C3HC4 viral protein ICP0. J Gen Virol 75:1223–1233

    CAS  PubMed  Google Scholar 

  • McKee BD, Handel MA (1993) Sex chromosomes, recombination, and chromatin conformation. Chromosoma 102:71–80

    CAS  PubMed  Google Scholar 

  • Melchior F (2000) SUMO—nonclassical ubiquitin. Annu Rev Cell Dev Biol 16:591–626

    Google Scholar 

  • Metzler-Guillemain C, Luciani J, Depetris D, Guichaoua MR, Mattei MG (2003) HP1beta and HP1gamma, but not HP1alpha, decorate the entire XY body during human male meiosis. Chromosome Res 11:73–81

    Article  CAS  PubMed  Google Scholar 

  • Muller S, Matunis MJ, Dejean A (1998) Conjugation with the ubiquitin-related modifier SUMO-1 regulates the partitioning of PML within the nucleus. EMBO J 17:61–70

    Article  CAS  PubMed  Google Scholar 

  • Muller S, Berger M, Lehembre F, Seeler JS, Haupt Y, Dejean A (2000) c-Jun and p53 activity is modulated by SUMO-1 modification. J Biol Chem 275:13321–13329

    Article  CAS  PubMed  Google Scholar 

  • Muller S, Ledl A, Schmidt D (2004) SUMO: a regulator of gene expression and genome integrity. Oncogene 23:1998–2008

    Article  PubMed  Google Scholar 

  • Pluta AF, Earnshaw WC, Goldberg IG (1998) Interphase-specific association of intrinsic centromere protein CENP-C with HDaxx, a death domain-binding protein implicated in Fas-mediated cell death. J Cell Sci 111:2029–2041

    CAS  PubMed  Google Scholar 

  • Richler C, Dhara SK, Wahrman J (2000) Histone macroH2A1.2 is concentrated in the XY compartment of mammalian male meiotic nuclei. Cytogenet Cell Genet 89:118–120

    Article  CAS  PubMed  Google Scholar 

  • Rodriguez MS, Desterro JM, Lain S, Midgley CA, Lane DP, Hay RT (1999) SUMO-1 modification activates the transcriptional response of p53. EMBO J 18:6455–6461

    Article  CAS  PubMed  Google Scholar 

  • Roeder GS, Bailis JM (2000) The pachytene checkpoint. Trends Genet 16:395–403

    Article  CAS  PubMed  Google Scholar 

  • Seeler JS, Dejean A (1999) The PML nuclear bodies: actors or extras? Curr Opin Genet Dev 9:362–367

    Article  CAS  PubMed  Google Scholar 

  • Seeler JS, Dejean A (2003) Nuclear and unclear functions of SUMO. Nat Rev Mol Cell Biol 4:690–699

    Article  CAS  PubMed  Google Scholar 

  • Seeler JS, Marchio A, Sitterlin D, Transy C, Dejean A (1998) Interaction of SP100 with HP1 proteins: a link between the promyelocytic leukemia-associated nuclear bodies and the chromatin compartment. Proc Natl Acad Sci USA 95:7316–7321

    Article  CAS  PubMed  Google Scholar 

  • Shaper NL, Wright WW, Shaper JH (1990) Murine beta 1,4-galactosyltransferase: both the amounts and structure of the mRNA are regulated during spermatogenesis. Proc Natl Acad Sci USA 87:791–795

    CAS  PubMed  Google Scholar 

  • Shen Z, Pardington-Purtymun PE, Comeaux JC, Moyzis RK, Chen DJ (1996) UBL1, a human ubiquitin-like protein associating with human RAD51/RAD52 proteins. Genomics 36:271–279

    Article  CAS  PubMed  Google Scholar 

  • Shiio Y, Eisenman RN (2003) Histone sumoylation is associated with transcriptional repression. Proc Natl Acad Sci USA 100:13225–13230

    Article  CAS  PubMed  Google Scholar 

  • Show MD, Folmer JS, Anway MD, Zirkin BR (2004) Testicular expression and distribution of the rat bcl2 modifying factor in response to reduced intratesticular testosterone. Biol Reprod 70:1153–1161

    CAS  PubMed  Google Scholar 

  • Solari AJ (1974) The behavior of the XY pair in mammals. Int Rev Cytol 38:273–317

    CAS  PubMed  Google Scholar 

  • Stead K, Aguilar C, Hartman T, Drexel M, Meluh P, Guacci V (2003) Pds5p regulates the maintenance of sister chromatid cohesion and is sumoylated to promote the dissolution of cohesion. J Cell Biol 163:729–741

    Article  CAS  PubMed  Google Scholar 

  • Stelter P, Ulrich HD (2003) Control of spontaneous and damage-induced mutagenesis by SUMO and ubiquitin conjugation. Nature 425:188–191

    Article  CAS  Google Scholar 

  • Strunnikov AV, Aravind L, Koonin EV (2001) Saccharomyces cerevisiae SMT4 encodes an evolutionarily conserved protease with a role in chromosome condensation regulation. Genetics 158:95–107

    CAS  PubMed  Google Scholar 

  • Suzuki H, Seki M, Kobayashi T, Kawabe Y, Kaneko H, Kondo N, Harata M, Mizuno S, Masuko T, Enomoto T (2001) The N-terminal internal region of BLM is required for the formation of dots/rod-like structures which are associated with SUMO-1. Biochem Biophys Res Commun 286:322–327

    Google Scholar 

  • Tanaka K, Nishide J, Okazaki K, Kato H, Niwa O, Nakagawa T, Matsuda H, Kawamukai M, Murakami Y (1999) Characterization of a fission yeast SUMO-1 homologue, pmt3p, required for multiple nuclear events, including the control of telomere length and chromosome segregation. Mol Cell Biol 19:8660–8672

    CAS  PubMed  Google Scholar 

  • Tarsounas M, Moens PB (2001) Checkpoint and DNA-repair proteins are associated with the cores of mammalian meiotic chromosomes. Curr Top Dev Biol 51:109–134

    Article  CAS  PubMed  Google Scholar 

  • Tarsounas M, Pearlman RE, Gasser PJ, Park MS, Moens PB (1997) Protein-protein interactions in the synaptonemal complex. Mol Biol Cell 8:1405–1414

    Google Scholar 

  • Walpita D, Plug AW, Neff NF, German J, Ashley T (1999) Bloom’s syndrome protein, BLM, colocalizes with replication protein A in meiotic prophase nuclei of mammalian spermatocytes. Proc Natl Acad Sci USA 96:5622–5627

    Article  CAS  PubMed  Google Scholar 

  • Wiltshire T, Park C, Caldwell KA, Handel MA (1995) Induced premature G2/M-phase transition in pachytene spermatocytes includes events unique to meiosis. Dev Biol 169:557–567

    Article  CAS  PubMed  Google Scholar 

  • Yan W, Santti H, Janne OA, Palvimo JJ, Toppari J (2003) Expression of the E3 SUMO-1 ligases PIASx and PIAS1 during spermatogenesis in the rat. Gene Expr Patterns 3:301–308

    Article  CAS  PubMed  Google Scholar 

  • Yang SH, Sharrocks AD (2004) SUMO promotes HDAC-mediated transcriptional repression. Mol Cell 13:611–617

    Article  CAS  PubMed  Google Scholar 

  • Zhong S, Hu P, Ye TZ, Stan R, Ellis NA, Pandolfi PP (1999) A role for PML and the nuclear body in genomic stability. Oncogene 18:7941–7947

    Article  CAS  PubMed  Google Scholar 

  • Zhong S, Muller S, Ronchetti S, Freemont PS, Dejean A, Pandolfi PP (2000a) Role of SUMO-1-modified PML in nuclear body formation. Blood 95:2748–2752

    CAS  PubMed  Google Scholar 

  • Zhong S, Salomoni P, Pandolfi PP (2000b) The transcriptional role of PML and the nuclear body. Nat Cell Biol 2:E85–E90

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Dr. Bill Wright for assistance in rat germ cell purification and Janet Folmer for assistance in preparing polyester wax testis sections. We also gratefully acknowledge Drs. Anne Pluta and Gerd Maul for their generosity in sharing antibody reagents and Dr. Pier Paolo Pandolfi for providing PML (−/−) mice for this study. This work was supported by grants from the National Institutes of Health awarded to M.J.M. (R01 GM60980) and to M.A.H. (R01 HD33816).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Michael J. Matunis.

Additional information

Communicated by E.A. Nigg

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rogers, R.S., Inselman, A., Handel, M.A. et al. SUMO modified proteins localize to the XY body of pachytene spermatocytes. Chromosoma 113, 233–243 (2004). https://doi.org/10.1007/s00412-004-0311-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00412-004-0311-7

Keywords

Navigation