Function of SPOC1 (PHF13) in meiotic sex chromsome inactivation (MSCI)

• Applicant: Professor Dr. Andreas Winterpacht
• Subject Area: Reproductive Medicine, Urology ; Human Genetics
• Term: from 2013 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 234738969

During the pachytene stage of male meiosis the X- and Y-chromosomes condense into a compact structure, called the XY-body. This coincides with a vast transcriptional silencing of the heterologous, unpaired regions of the sex chromosomes. This process is called meiotic sex chromosome inactivation (MSCI). Disturbances in this process result in a breakdown of spermatogenesis. SPOC1 (PHF13) is a recently identified protein which associates with chromatin and plays a role in writing and reading of epigenetic marks. Using Spoc1-/- mice we were able to demonstrate that loss of SPOC1 results in impaired spermatogenesis and infertility. Genome wide expression studies revealed overexpression of genes on the X- and Y-chromosome during meiosis of Spoc1-/- mice. Consequently, we hypothesize that SPOC1 is involved in proper MSCI via epigenetic mechanisms. In the present proposal we intend to prove this hypothesis by means of immuncytochemical investigations and genome wide epigenetic analysis. Despite the function of SPOC1 during spermatogenesis the expected results will shed light on the (epigenetic) mechanism of MSCI, for which very limited data have been available so far.

• DFG Programme: Research Grants