Background: HP1γ, a well-known regulator of gene expression, has been recently identified to be a target of Aurora A, a mitotic kinase which is important for both gametogenesis and embryogenesis. The purpose of this study was to define whether the Aurora A-HP1γ pathway supports cell division of gametes and/or early embryos, using western blot, immunofluorescence, immunohistochemistry, electron microscopy, shRNA-based knockdown, site-directed mutagenesis, and Affymetrix-based genome-wide expression profiles. Results: We find that the form of HP1γ phosphorylated by Aurora A, P-Ser83 HP1γ, is a passenger protein, which localizes to the spermatozoa centriole and axoneme. In addition, disruption in this pathway causes centrosomal abnormalities and aberrations in cell division. Expression profiling of male germ cell lines demonstrates that HP1γ phosphorylation is critical for the regulation of mitosis-associated gene expression networks. In female gametes, we observe that P-Ser83-HP1γ is not present in meiotic centrosomes of M2 oocytes, but after syngamy, it becomes detectable during cleavage divisions, coinciding with early embryonic genome activation. Conclusions: These results support the idea that phosphorylation of HP1γ by Aurora A plays a role in the regulation of gene expression and mitotic cell division in cells from the sperm lineage and in early embryos. Combined, this data is relevant to better understanding the function of HP1γ in reproductive biology.
Bibliographical noteFunding Information:
This work was supported by funding, from the National Institutes of Health (grants R01 CA178627 to GL, R01 DK52913 to RU and T32CA148073 to AG), the Mayo Foundation, as well as the Mayo Clinic Center for Cell Signaling in Gastroenterology (P30DK084567) and a Career Development Award from the Mayo Clinic SPORE in Pancreatic Cancer (P50 CA102701, both to GL).
© 2015 Leonard et al.; licensee BioMed Central.
- Embryonic genome activation
- Heterochromatin Protein 1
- Preimplantation embryo