title: SUMO-1, human male germ cell development, and the androgen receptor in the testis of men with normal and abnormal spermatogenesis.
abstract: Sumoylation affects multiple cellular events, including chromatin inactivation and transcriptional repression. Our data provide the first characterization of small ubiquitin-related modifier-1 (SUMO-1) expression during human spermatogenesis by the use of high-resolution cellular SUMO-1 bioimaging. During human meiotic prophase, SUMO-1 localizes to sex chromosomes and centromeric and pericentromeric chromatin. As human spermatocytes progress toward the end of prophase in meiosis I, SUMO-1 is no longer detected within the sex body and pericentromeric heterochromatin but localizes exclusively to centromeres. SUMO-1 localization along sex chromosome axes, pseudoautosomal region, and centromeres of both chromosomes supports a role for SUMO-1 sumoylation in epigenetic events occurring over the entire sex body, e.g., meiotic sex chromosome inactivation and chromatin condensation. Centromeric SUMO-1 throughout meiotic prophase suggests a role in centromeric chromatin condensation and/or other centromere/kinetochore functions. SUMO-1 is likely involved in both facultative and constitutive heterochromatin processes in spermatocytes. Haploid round spermatids show a consistent association of SUMO-1 with centromeric clusters. During spermatid elongation, SUMO-1 localizes in the manchette perinuclear ring. Steroidogenic Leydig cells show some cytoplasmic but strong nuclear and perinuclear SUMO-1. Peritubular myoepithelial cell SUMO-1 colocalizes with centromeric heterochromatin. In epithelial Sertoli cells, when associated with centromeric heterochromatin, SUMO-1 is adjacent but not colocalized with the nucleolus. Male germ cells demonstrate no SUMO-1 nucleolar association. Human and rodent Sertoli cells consistently show an inverse correlation between androgen receptor (AR) and SUMO-1 expression and compartmentalization. Sertoli cells from certain infertile patients, however, showed greatly decreased SUMO-1 and AR. Our data suggest that human testicular SUMO-1 has specific functions in heterochromatin organization, meiotic centromere function, and gene expression.
authors.affiliation: Center for Biomedical Research, Population Council, New York, New York, USA.
authors.forename: Margarita
authors.initials: M
authors.lastname: Vigodner
authors.forename: Tomomoto
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Peter N
authors.initials: PN
authors.lastname: Schlegel
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Morris
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D002503:Centromere / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000032:analysis; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D007248:Infertility, Male / Q000378:metabolism*; D007985:Leydig Cells / Q000378:metabolism; D008297:Male; D051379:Mice; D008856:Microscopy, Fluorescence; D051381:Rats; D011944:Receptors, Androgen / Q000378:metabolism*; D025842:SUMO-1 Protein; D012708:Sertoli Cells / Q000378:metabolism; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D013091:Spermatogenesis / Q000502:physiology*; D013094:Spermatozoa / Q000378:metabolism; D013737:Testis / Q000166:cytology / Q000378:metabolism*
chemical_list: D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D011944:Receptors, Androgen; D025842:SUMO-1 Protein; C495501:SUMO1 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; C047458:fibrillarin