TY - JOUR
T1 - The Aurora A-HP1γ pathway regulates gene expression and mitosis in cells from the sperm lineage
AU - Leonard, Phoebe H.
AU - Grzenda, Adrienne
AU - Mathison, Angela
AU - Morbeck, Dean E.
AU - Fredrickson, Jolene R.
AU - De Assuncao, Thiago M.
AU - Christensen, Trace
AU - Salisbury, Jeffrey
AU - Calvo, Ezequiel
AU - Iovanna, Juan
AU - Coddington, Charles C.
AU - Urrutia, Raul
AU - Lomberk, Gwen
N1 - Publisher Copyright:
© 2015 Leonard et al.; licensee BioMed Central.
PY - 2015/5/29
Y1 - 2015/5/29
N2 - 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.
AB - 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.
KW - CBX3
KW - Embryonic genome activation
KW - Epigenetics
KW - Gametes
KW - HP1γ
KW - Heterochromatin Protein 1
KW - Meiosis
KW - Mitosis
KW - Preimplantation embryo
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U2 - 10.1186/s12861-015-0073-x
DO - 10.1186/s12861-015-0073-x
M3 - Article
C2 - 26021315
AN - SCOPUS:84930204241
SN - 1471-213X
VL - 15
JO - BMC Developmental Biology
JF - BMC Developmental Biology
IS - 1
M1 - 23
ER -