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Sumoylation precedes accumulation of phosphorylated H2AX on sex chromosomes during their meiotic inactivation

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Abstract

During meiosis in male mammals, X and Y chromosomes undergo the process of meiotic sex chromosome inactivation (MSCI). A crucial role in MSCI has recently been reported for BRCA1, ATR kinase, and phosphorylated histone H2AX, but the exact mechanism remains to be determined. Small ubiquitin-like modifier (SUMO) proteins have recently been shown to localize to the sex body in mouse meiotic spermatocytes, but the role they play during MSCI is unknown. In this study, in order to better understand the molecular events of MSCI, we followed dynamic changes in γH2AX and SUMO localization patterns during MSCI. Using confocal laser scanning microscopy (CLSM) as an analytical tool for visualizing numerous spermatocytes from the same development stage and for consecutively following the meiotic progression, we were able to demonstrate a very early appearance of SUMO-1, which preceded γH2AX accumulation on the sex chromosomes during their meiotic inactivation. In contrast to SUMO-1, SUMO-2/3 was undetectable in zygotene spermatocytes, suggesting a possible specific role for SUMO-1 in the initiation of MSCI.

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Abbreviations

ATR:

ATM and Rad3-related

BRCA1:

breast cancer 1, early onset

BSA:

bovine serum albumin

CLSM:

confocal laser scanning microscopy

CY:

cyanine

DSB:

double strand breaks

E sp:

elongating spermatids

FITC:

fluorescein isothiocyanate

γH2AX:

phosphorylated histone H2AX

MSCI:

meiotic sex chromosome inactivation

MSUC:

meiotic silencing of unsynapsed chromatin

PAR:

pseudoautosomal region

PBS:

phosphate-buffered saline

PI:

propidium iodide

PL:

preleptotene spermatocytes

Le:

leptotene spermatocytes

Meio:

meiotic figures

PS:

pachytene spermatocytes

RS:

round spermatids

Se:

Sertoli cells

Sg:

spermatogonia

SC:

synaptonemal complex

SUMO:

small ubiquitin-like modifier(s)

Zyg:

zygotene spermatocytes

References

  • Ayaydin F, Dasso M (2004) Distinct in vivo dynamics of vertebrate SUMO paralogues. Mol Biol Cell 15:5208–5218

    Article  PubMed  CAS  Google Scholar 

  • Baarends WM, Wassenaar E, van der Laan R et al (2005) Silencing of unpaired chromatin and histone H2A ubiquitination in mammalian meiosis. Mol Cell Biol 25(3):1041–1053

    Article  PubMed  CAS  Google Scholar 

  • Bellani MA, Romanienko PJ, Cairatti DA, Camerini-Otero RD (2005) SPO11 is required for sex-body formation, and Spo11 heterozygosity rescues the prophase arrest of Atm−/− spermatocytes. J Cell Sci 118:3233–3245

    Article  PubMed  CAS  Google Scholar 

  • Bohren KM, Nadkarni V, Song JH, Gabbay KH, Owerbach D (2004) M55V polymorphism in a novel SUMO gene (SUMO-4) differentially activates heat shock transcription factors and is associated with susceptibility to type I diabetes mellitus. J Biol Chem 279(26):27233–27238

    Article  PubMed  CAS  Google Scholar 

  • Cheng CH, Lo YH, Liang SS et al (2006) SUMO modifications control assembly of synaptonemal complex and polycomplex in meiosis of Saccharomyces cerevisiae. Genes Dev 20(15):2067–2081

    Article  PubMed  CAS  Google Scholar 

  • Cohen PE, Pollack SE, Pollard JW (2006) Genetic analysis of chromosome pairing, recombination, and cell cycle control during first meiotic prophase in mammals. Endocr Rev 27(4):398–426

    Article  PubMed  CAS  Google Scholar 

  • Fernandez-Capetillo O, Mahadevaiah SK, Celeste A et al (2003) H2AX is required for chromatin remodeling and inactivation of sex chromosomes in male mouse meiosis. Dev Cell 4:497–508

    Article  PubMed  CAS  Google Scholar 

  • Gill G (2004) SUMO and ubiquitin in the nucleus: different functions, similar mechanisms? Genes Dev 18:2046–2059

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Johnson ES (2004) Protein modification by SUMO. Annu Rev Biochem 73:355–382

    Article  PubMed  CAS  Google Scholar 

  • La Salle S, Sun F, Zhang XD, Matunis MJ, Handel MA (2008) Developmental control of sumoylation pathway proteins in mouse male germ cells. Dev Biol 321(1):227–237

    Article  PubMed  CAS  Google Scholar 

  • Mahadevaiah SK et al (2001) Recombinational DNA double-strand breaks in mice precede synapsis. Nat Genet 27:271–276

    Article  PubMed  CAS  Google Scholar 

  • Mahadevaiah SK, Bourc'his D, de Rooij DG, Bestor TH, Turner JM, Burgoyne PS (2008) Extensive meiotic asynapsis in mice antagonises meiotic silencing of unsynapsed chromatin and consequently disrupts meiotic sex chromosome inactivation. J Cell Biol 182(2):263–276

    Article  PubMed  CAS  Google Scholar 

  • Martin RH (2008) Meiotic errors in human oogenesis and spermatogenesis. Reprod Biomed Online 16(4):523–531

    Article  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  CAS  Google Scholar 

  • Russell L, Ettlin R, Sinha Hikim A, Clegg E (eds) (1990) Histological and Histopathological evaluation of the testis. Cache River, Clearwater, FL

  • Sacher M, Pfander B, Hoege C, Jentsch S (2006) Control of Rad52 recombination activity by double-strand break-induced SUMO modification. Nat Cell Biol 11:1284–1290

    Article  CAS  Google Scholar 

  • Schwartz DC, Hochstrasser M (2003) A superfamily of protein tags: ubiquitin, SUMO and related modifiers. Trends Biochem Sci 28:321–328

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Turner JM (2007) Meiotic sex chromosome inactivation. Development 134(10):1823–1831

    Article  PubMed  CAS  Google Scholar 

  • Turner JM, Aprelikova O, Xu X et al (2004) BRCA1, histone H2AX phosphorylation and male meiotic sex chromosome inactivation. Curr Biol 14:2135–2142

    Article  PubMed  CAS  Google Scholar 

  • Turner JM, Mahadevaiah SK, Fernandez-Capetillo O et al (2005) Silencing of unsynapsed meiotic chromosomes in the mouse. Nat Genet 37(1):41–47

    PubMed  CAS  Google Scholar 

  • Vertegaal AC, Ogg SC, Jaffray E et al (2004) A proteomic study of SUMO-2 target proteins. J Biol Chem 279(32):33791–33798

    Article  PubMed  CAS  Google Scholar 

  • Vigodner M, Morris PL (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

    Article  PubMed  CAS  Google Scholar 

  • Vigodner M, Lewin LM, Glaser T, Shochat L, Mittelman L, Golan R (2002) Use of confocal microscopy for the study of spermatogenesis. Methods Cell Sci 24(4):169–180

    Article  PubMed  Google Scholar 

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Acknowledgments

The author thanks Stern College for Women, Yeshiva University and Joseph Alexander Foundation for supporting this research project; Dr. Alison North and other staff of The Rockefeller University Bio-Imaging Resource Center kindly provided help with the use of the facility’s equipment.

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  1. Department of Biology, Stern College, Yeshiva University, New York, 245 Lexington Ave, New York, NY, 10016, USA

    Margarita Vigodner

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  1. Margarita Vigodner
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Correspondence to Margarita Vigodner.

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Responsible Editor: Herbert McGregor.

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Vigodner, M. Sumoylation precedes accumulation of phosphorylated H2AX on sex chromosomes during their meiotic inactivation. Chromosome Res 17, 37–45 (2009). https://doi.org/10.1007/s10577-008-9006-x

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  • DOI: https://doi.org/10.1007/s10577-008-9006-x

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