Regulated expression of the ubiquitin protein ligase, E3Histone/LASU1/Mule/ARF-BP1/HUWE1, during spermatogenesis.

A ubiquitin protein ligase (E3), E3^Histone/LASU1 (Mule/ARF-BP1/HUWE1), was recently identified that mediates ubiquitination of core histones, the Mcl-1 anti-apoptotic protein, and the p53 tumor suppressor protein. However, the expression of E3^Histone/LASU1 remains poorly studied. Because we identified E3^Histone/LASU1 from the testis, we explored its regulation during spermatogenesis. In the first wave of rat spermatogenesis, E3^Histone/LASU1 mRNA and protein had peak expression at days 10 and 20, respectively, and decreased with age. Consistent with these findings, immunohistochemistry revealed that E3^Histone/LASU1 was highly expressed in nuclei from spermatogonia to mid-pachytene spermatocytes. There was no obvious staining in spermatids, when histones are ubiquitinated and degraded. E3^Histone/LASU1 was also expressed in other tissues. However, except in neuronal cells of the brain, expression was cytoplasmic. Thus, E3^Histone/LASU1 may play a role in chromatin modification in early germ cells of the testis, but also has functions in other tissues. Developmental Dynamics 236:2889-2898, 2007. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]