The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2018

Gene expression profiling of epigenetic chromatin modification enzymes, chromatin remodelling factors and ubiquitination enzymes in Dcaf17 knockout mouse testis (#368)

Bhavesh Mistry 1 , Maha Alanazi 1 , Mohamed Rajab 1 , Abdullah Assiri 1
  1. King Faisal Specialist Hospital and Research Centre, Riyadh, Riyadh, RIYADH, Saudi Arabia

The DDB1– and CUL4–associated factor 17 (DCAF17) is a member of DCAF family proteins that act as substrate receptors for Cullin-4 (CUL4) based E3 ubiquitin ligase complexes (CRLs) and regulate selective ubiquitylation of proteins. In Human, mutations in DCAF17 encoding gene cause a rare autosomal recessive genetic disorder known as Woodhouse-Sakati Syndrome (WSS), which is characterized by hypogonadism, partial alopecia, diabetes mellitus, mental retardation, and deafness. Recently, it has been shown that loss of DCAF17 in mice caused male infertility due to defective spermatogenesis. The Dcaf17-/- mice produced low number of sperm with abnormal shape and significantly low motility. Testis of Dcaf17 KO mouse displayed defects in nuclear compaction, acrosome biogenesis, and manchette assembly in spermatids and mature sperm. CRLs play critical roles in regulation of normal spermatogenesis. However, the molecular function of DCAF17 in normal sperm biogenesis is not known. Using quantitative real-time PCR and Western blot techniques, we show abnormal expression pattern of several epigenetic chromatin modification enzymes, chromatin remodelling factors and ubiquitylation enzymes in the Dcaf17 KO mouse testis. The aberrant expression of the different chromatin modification enzymes, chromatin remodelling factors and ubiquitylation enzymes due to the loss of DCAF17 suggests that DCAF17 may play a critical role in chromatin compaction, an important aspect of sperm development. These data provide a rich resource for further elucidating the cellular/molecular mechanisms of DCAF17 in chromatin compaction that may contribute to the onset of male infertility.