SUMO-1, human male germ cell development, and the androgen receptor in the testis of men with normal and abnormal spermatogenesis.

摘要

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.