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Hum. Reprod. Advance Access published online on August 10, 2008
Human Reproduction, doi:10.1093/humrep/den300
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© The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
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Small ubiquitin-related modifier (SUMO)-1, SUMO-2/3 and SUMOylation are involved with centromeric heterochromatin of chromosomes 9 and 1 and proteins of the synaptonemal complex during meiosis in men

Petrice W. Brown1, KeumSil Hwang1, Peter N. Schlegel1,2 and Patricia L. Morris1,2,3,4

1 Center for Biomedical Research, Population Council, 1230 York Avenue, New York, NY, 10065, USA 2 Department of Urology, Weill Cornell Medical Center, New York, NY, USA 3 The Rockefeller University, New York, NY, USA

4 Correspondence address. Tel: +1-212-327-8756; Fax: +1-212-327-7678; E-mail: p-morris{at}popcbr.rockefeller.edu

BACKGROUND: Post-transcriptional modification by SUMOylation is involved in numerous cellular processes including human spermatogenesis. For human male meiosis, we previously showed that the small ubiquitin-related modifier-1 (SUMO-1) protein localizes to chromatin axes in early pachytene spermatocytes, then to kinetochores as meiosis progresses. Here, we delineate possible functional roles based on subcellular localization for SUMO-1 and SUMO-2/3.

METHODS: Western and immunoprecipitation analyses were conducted on proteins isolated from the testis of two normal adult fertile men. Combinatorial immunofluorescence and chromosome-specific fluorescence in situ hybridization analyses were performed on male meiocytes obtained during testicular biopsy from four patients undergoing testicular sperm extraction for assisted reproduction technologies.

RESULTS: The synaptonemal complex (SC) and SC proteins (SCP)-1 and SCP2, but not SCP3, are SUMOylated by SUMO-1 during the pachytene substage. Likewise, two distinct localization patterns for SUMO-1 are identified: a linear pattern co-localized with autosomal SCs and isolated SUMO-1 near the centromeric heterochromatin of chromosomes 9 and 1. In contrast to SUMO-1, which is not detectable prior to pachytene in normal tissue, SUMO-2/3 is identified as early as leptotene and zygotene and in some, but not all, pachytene cells; no linear patterns were detected. Similar to SUMO-1, SUMO-2/3 localizes in two predominant subnuclear patterns: a single, dense signal near the centromere of human chromosome 9 and small, individual foci co-localized with autosomal centromeres.

CONCLUSIONS: Our data suggest that SUMO-1 may be involved in maintenance and/or protection of the autosomal SC. SUMO-2/3, though expressed similarly, may function separately and independently during pachytene in men.

Key words: small ubiquitin-related modifier-1/men/meiosis/heterochromatin/chromosome

Submitted on March 10, 2008; resubmitted on June 6, 2008; accepted on July 11, 2008.


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