The Aurora A-HP1γ pathway regulates gene expression and mitosis in cells from the sperm lineage

BMC Developmental Biology

Gwen Lomberk⁵  Raul Urrutia⁶  Charles C. Coddington⁷  Juan Iovanna¹  Ezequiel Calvo³  Jeffrey Salisbury⁴  Trace Christensen⁴  Thiago M. de Assuncao²  Jolene R. Fredrickson⁷  Dean E. Morbeck⁷  Angela Mathison²  Adrienne Grzenda⁴  Phoebe H. Leonard⁷ 

[1]Centre de Recherché en Cancérologie de Marseille (CRCM), Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 624, Stress Cellulaire, 163 Avenue de Luminy, Case 915, Parc Scientifique et Technologique de Luminy, Marseille Cedex 9 13288, France

[2]Department of Medicine, Mayo Clinic, Laboratory of Epigenetics and Chromatin Dynamics, Gastroenterology Research Unit, Guggenheim 10, 200 First Street SW, Rochester 55905, MN, USA

[3]Molecular Endocrinology and Oncology Research Center, Centre Hospitalier de l’Universite Laval (CHUL) Research Center, Quebec G1V 4G2, QC, Canada

[4]Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester 55905, MN, USA

[5]Department of Obstetrics and Gynecology, Mayo Clinic, Rochester 55905, MN, USA

[6]Translational Epigenomics Program, Center for Individualized Medicine, Rochester 55905, MN, USA

[7]Division of Reproductive Endocrinology and Infertility, Mayo Clinic, Rochester 55905, MN, USA

关键词: Embryonic genome activation;    Mitosis;    Meiosis;    Preimplantation embryo;    Gametes;    CBX3;    HP1γ;    Heterochromatin Protein 1;    Epigenetics;   

Others  :  1209034
DOI  :  10.1186/s12861-015-0073-x

 received in 2014-06-20, accepted in 2015-05-12,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Leonard et al.; licensee BioMed Central.

【 图 表 】

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