1. ¹Institut für Humangenetik, Universitätsklinikum Essen, Essen, Germany
2. ²Abteilung für Andrologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg-Eppendorf, Germany
3. ³Zentrum für Kinderheilkunde, Universitätsklinikum Essen, Essen, Germany

Correspondence: Professor B Horsthemke, Institut für Humangenetik, Universitätsklinikum Essen, Hufelandstr 55, Essen D-45122, Germany. Tel: +49 201 723 4556; Fax: +49 201 723 4556; E-mail: bernhard.horsthemke@uni-due.de

Received 5 March 2009; Revised 17 April 2009; Accepted 23 April 2009; Published online 27 May 2009.

Abstract

The imprinted domain in human 15q11-q13 is controlled by a bipartite imprinting centre (IC), which overlaps the 5' part of the paternally expressed SNURF–SNRPN gene. We have recently described two novel genes upstream of SNURF–SNRPN (PWRN1 and PWRN2), which are biallelically expressed in the testis. We have now found that PWRN1 represents an alternative 5' part of SNURF–SNRPN, and that its expression in the brain is imprinted. To determine when the locus is activated during spermatogenesis and which factors are involved in this process, we have mined gene-expression data of testicular biopsies from men with different types of spermatogenic failure. Whereas PWRN1–SNURF–SNRPN and PWRN2 are expressed in post-meiotic germ cells only, a hitherto undetected SNURF–SNRPN upstream transcript is expressed already at meiosis. Several epigenetic factors (eg, MBD1 and MBD2 isoforms, MBD3L1, SUVH39H2, BRDT, and EZH2) are upregulated at specific stages of spermatogenesis, suggesting that they play an important role in the epigenetic reprogramming during spermatogenesis.