Hostname: page-component-5447f9dfdb-tm5m8 Total loading time: 0 Render date: 2025-07-29T04:00:12.184Z Has data issue: false hasContentIssue false
  • English
  • Français

Localization and expression of peptidylarginine deiminase 4 (PAD4) in mammalian oocytes and preimplantation embryos

Published online by Cambridge University Press:  30 November 2011

Manjula Brahmajosyula  and
Masashi Miyake
Manjula Brahmajosyula
Affiliation:
Department of Bioresource Science, Graduate School of Agricultural Science, Kobe University, 1–1 Rokkodai-cho, Nada-ku, Kobe 657–8501, Japan.
Masashi Miyake*
Affiliation:
Department of Bioresource Science, Graduate School of Agricultural Science, Kobe University, 1–1 Rokkodai-cho, Nada-ku, Kobe 657–8501, Japan. Organization of Advanced Science and Technology, Kobe University, 1–1 Rokkodai-cho, Nada-ku, Kobe 657–8501, Japan.
*
All correspondence to: Masashi Miyake. Department of Bioresource Science, Graduate School of Agricultural Science, Kobe University, 1–1 Rokkodai-cho, Nada-ku, Kobe 657–8501, Japan. Tel: +81 78 803 5807. Fax: +81 78 803 6581. e-mail: miyake@kobe-u.ac.jp
Get access Rights & Permissions [Opens in a new window]

Summary

Post-translational modifications generally involve the addition or removal of various functional groups to or from the protein residues. However, citrullination, which is catalyzed by the peptidylarginine deiminases (PADs), involves conversion of one kind of amino acid residue into another. One of five isoforms, PAD4 is a nuclear enzyme known to play a role in development, differentiation and apoptosis through gene regulation. To investigate the possible role of PAD4 in mammalian preimplantation embryonic development, we first studied localization and expression of PAD4 and citrullinated proteins in pig and mouse oocytes, and parthenogenetic or in vitro fertilized (IVF) embryos. Immunofluorescence study revealed that PAD4 primarily localizes in the cytoplasm in pig oocytes and parthenogenetic embryos. However, the nuclear translocation of PAD4 was observed in late germinal vesicle (GV) stage oocytes prior to GV breakdown and was localized around the metaphase (M)I and II spindle. Nucleus localized PAD4 was noticed partially again in blastocysts. In mouse IVF embryos, nuclear translocation started from the 2-cell stage and gradually increased up to blastocyst. Western blot studies confirmed that PAD4 was expressed in oocytes, and parthenogenetic embryos of pig. Citrullinated proteins were detected in granular form on the chromatin in GV, MI and MII oocytes and nuclei in all the stages of the embryos studied. It was found that the target of citrullination was histone protein (H3), not B23. Therefore the presence of PAD4 and citrullinated histone H3 in oocytes and embryos suggested a possible role for PAD4 in preimplantation embryonic development.

Keywords

CitrullinationIVF embryosMousePAD4ParthenotesPig

Information

Type
Research Article
Information
Zygote , Volume 21 , Issue 4 , November 2013 , pp. 314 - 324
Copyright
Copyright © Cambridge University Press 2011 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

References

Borer, R.A., Lehner, C.F., Eppenberger, H.M. & Nigg, E.A. (1989). Major nucleolar proteins shuttle between nucleus and cytoplasm. Cell 56, 379–90.CrossRefGoogle ScholarPubMed
Chatot, C.L., Ziomek, C.A., Bavister, B.D., Lewis, J.L. & Torres, I. (1989). An improved culture medium supports development of random-bred 1-cell mouse embryos in vitro. J. Reprod. Fertil. 86, 679–88CrossRefGoogle ScholarPubMed
Chavanas, S., Mechin, M.C., Takahara, H., Kawada, A., Nachat, R., Serre, G. & Simon, M. (2004). Comparative analysis of the mouse and human peptidylarginine deiminase gene clusters reveals highly conserved non-coding segments and a new gene, PADI6. Gene 330, 19–27.CrossRefGoogle Scholar
Cuthbert, G.L., Daujat, S., Snowden, A.W., Erdjument-Bromage, H., Hagiwara, T., Yamada, M., Schneider, R., Gregory, P.D., Tempst, P., Bannister, A.J. & Kouzarides, T. (2004). Histone deimination antagonizes arginine methylation. Cell 118, 545–53.CrossRefGoogle ScholarPubMed
Gallicano, G.I., Larabell, C.G., McGaughey, R.W. & Capco, D.G. (1994). Novel cytoskeletal elements in mammalian eggs are composed of a unique arrangement of intermediate filaments. Mech. Dev. 45, 211–26.CrossRefGoogle ScholarPubMed
Guerrin, M., Ishigami, A., Méchin, M.C., Nachat, R., Valmary, S., Sebbag, M., Simon, M., Senshu, T. & Serre, G. (2003). cDNA cloning, gene organization and expression analysis of human peptidylarginine deiminase type I. Biochem. J. 370, 167–74.CrossRefGoogle ScholarPubMed
Hagiwara, T., Nakashima, K., Hirano, H., Senshu, T. & Yamada, M. (2002). Deimination of arginine residues in nucleophosmin/B23 and histones in HL-60 granulocytes. Biochem. Biophys. Res. Comm. 290, 979–83.CrossRefGoogle ScholarPubMed
Hansen, J.C. (2002). Conformational dynamics of the chromatin fiber in solution: determinants, mechanisms, and functions. Annu. Rev. Biophys. Biomol. Struct. 31, 361–92.CrossRefGoogle ScholarPubMed
Henery, C.C., Miranda, M., Wiekowski, M., Wilmut, I. & DePamphilis, M.L. (1995). Repression of gene expression at the beginning of mouse development. Dev. Biol. 169, 448–60CrossRefGoogle ScholarPubMed
Hyttel, P., Laurincik, J., Rosenkranz, Ch., Rath, D., Niemann, H., Ochs, R.L. & Schellander, K. (2000). Nucleolar proteins and ultrastructure in preimplantation porcine embryos developed in vivo. Biol. Reprod. 63, 1848–56.CrossRefGoogle ScholarPubMed
Ishigami, A., Ohsawa, T., Asaga, H., Akiyama, K., Kuramoto, M. & Maruyama, N. (2002). Human peptidylarginine deiminase type II: molecular cloning, gene organization, and expression in human skin. Arch. Biochem. Biophys. 407, 25–31.CrossRefGoogle ScholarPubMed
Kanno, T., Kawada, A., Yamamouchi, J., Yosida-Noro, C., Yoshiki, A., Shiraiwa, M., Kusakabe, M., Manabe, M., Tezuka, T. & Takahara, H. (2000). Human peptidylarginine deiminase type I: molecular cloning and nucleotide sequence of the cDNA, properties of the recombinant enzyme, and immunohistochemical localization in human skin. J. Invest. Dermat. 115, 813–23.CrossRefGoogle Scholar
Kure-bayashi, S., Miyake, M., Katayama, M., Miyano, T. & Kato, S. (1996). Development of porcine blastocysts from in vitro-matured and activated haploid and diploid oocytes. Theriogenology 46, 1027–36.CrossRefGoogle ScholarPubMed
Kure-bayashi, S., Miyake, M., Okada, K. & Kato, S. (2000). Successful implantation of in vitro-matured, electro-activated oocytes in the pig. Theriogenology 46, 1105–19.CrossRefGoogle Scholar
Li, E. (2002). Chromatin modification and epigenetic reprogramming in mammalian development. Nature Rev. Genet. 9, 662–73.CrossRefGoogle Scholar
Mastronardi, F.G., Wood, D.D., Mei, J., Raijmakers, R., Tseveleki, V., Dosch, H.M., Probert, L., Casaccia-Bonnefil, P. & Moscarello, M.A. (2006). Increased citrullination of histone H3 in multiple sclerosis Brain and animal models of demyelination: a role for tumor necrosis factor-induced peptidylarginine deiminase 4 translocation. J. Neurosci. 26, 11387–96.CrossRefGoogle ScholarPubMed
Mattioli, M., Galeati, G., Bacci, M.L. & Seren, E (1988). Follicular factors influence oocyte fertilizability by modulating the intercellular cooperation between cumulus cell and oocyte. Gamete Res. 21 223–32CrossRefGoogle ScholarPubMed
Moore, R.M. & Trounson, A.R. (1977). Hormonal and follicular factors affecting maturation of sheep oocytes in vitro and their subsequent developmental capacity. J. Reprod. Fertil. 49, 101–9.CrossRefGoogle Scholar
Nakashima, K., Hagiwara, T., Ishigami, A., Nagata, S., Asaga, H., Kuramoto, M., Senshu, T. & Yamada, M. (1999). Molecular characterization of Peptidylarginine deiminase in HL-60 cells induced by retinoic acid and 1α 25- dihydroxyvitamin D3. J. Biol. Chem. 274, 27786–92.CrossRefGoogle Scholar
Nakashima, K., Hagiwara, T. & Yamada, M. (2002). Nuclear localization of peptidylarginine deiminase V and histone deimination in granulocytes. J. Biol. Chem. 277, 49562–68.CrossRefGoogle ScholarPubMed
Quinn, P., Kerin, J.F. & Warnes, G.M. (1985). Improved pregnancy rate in human in vitro fertilization with the use of a medium based on the composition of human tubal fluid. Fertil. Steril. 44, 493–98.CrossRefGoogle Scholar
Raijmakers, R., Zendman, A.J.W., Egberts, W.V., Vossenaar, E.R., Raats, J., Soede-Huijbregts, C., Rutjes, F.P.J.T., van Veelen, P.A., Drijfhout, J.W. & Pruijn, G.J.M (2007). Methylation of arginine residues interferes with citrullination by peptidylarginine deiminases in vitro. J. Mol. Biol. 367, 1118–29.CrossRefGoogle ScholarPubMed
Reik, W., Dean, W. & Walter, J. (2001). Epigenetic reprogramming in mammalian development. Sci. Rev. 293, 1089–93.Google ScholarPubMed
Sarmento, O.F., Digilio, L.C., Wang, Y., Perlin, J., Herr, J.C., Allis, C.D. & Coonrod, S.A. (2004). Dynamic alterations of specific histone modifications during early murine development. J. Cell Sci. 117, 4449–59.CrossRefGoogle ScholarPubMed
Scheer, U., Thiry, M. & Goessens, G. (1993). Structure, function and assembly of the nucleolus. Trends Cell Biol. 3, 236–41.CrossRefGoogle ScholarPubMed
Senshu, T., Kan, S., Ogawa, H., Manabe, M. & Asaga, H. (1996). Preferential deimination of keratin K1 and filaggrin during the terminal differentiation of human epidermis. Biochem. Biophys. Res. Commun. 225, 712–19.CrossRefGoogle ScholarPubMed
Spector, D.L., Ochs, R.L. & Busch, H. (1984). Silver staining, immunofluorescence and immunoelectron microscopic localization of nucleolar phosphoproteins B23 and C23. Chromosoma 90, 139–48.CrossRefGoogle ScholarPubMed
Svarcova, O., Dinnyes, A., Polgar, Z., Bodo, S., Adorjan, M., Meng, Q. & Maddox-Hyttel, P. (2009). Nucleolar re-activation is delayed in mouse embryos cloned from two different cell lines. Mol. Reprod. Dev. 76,132–41.CrossRefGoogle ScholarPubMed
Szebeni, A. & Olson, M.O.J. (1999). Nucleolar protein B23 has molecular chaperone activities. Protein Sci. 8, 905–12.CrossRefGoogle ScholarPubMed
Tarcsa, E., Marekov, L.N., Mei, G., Melino, G., Lee, S.C. & Steinert, P.M. (1996). Protein unfolding by peptidylarginine deiminase. Substrate specificity and structural relationships of the natural substrates trichohyalin and filaggrin. J. Biol. Chem. 271, 30709–16.CrossRefGoogle ScholarPubMed
Thuan, N.V., Harayama, H. & Miyake, M. (2002). Characteristics of preimplantational development of porcine parthenogenetic diploids relative to the existence of amino acids in vitro. Biol. Reprod. 67, 1688–98.CrossRefGoogle Scholar
Vossenaar, E.R., Zendman, A.J.W., Venrooij, W.J. & Pruijn, G.J.M. (2003). PAD, a growing family of citrullinating enzymes: genes, features and involvement in disease. BioEssays 25, 1106–18.CrossRefGoogle ScholarPubMed
Wang, Y., Wysocka, J., Sayegh, J., Lee, Y.H., Perlin, J.R., Leonelli, L., Sonbuchner, L.S., McDonald, C.H., Cook, R.G., Dou, Y., Roeder, R.G., Clarke, S., Stallcup, M.R., Allis, C.D. & Coonrod, S.A. (2004). Human PAD4 regulates histone arginine methylation levels via demethylimination. Science 306, 279–83.CrossRefGoogle ScholarPubMed
Wang, Y., Li, M., Stadler, S., Correll, S., Li, P., Wang, D., Hayama, R., Leonelli, L., Han, H., Grigoryev, S.A., Allis, C.D. & Coonrod, S.A. (2009). Histone hypercitrullination mediates chromatin decondensation and neutrophil extracellular trap formation. J. Cell Biol. 184, 205–13.CrossRefGoogle ScholarPubMed
Watson, A.J., Kidder, G.M. & Schultz, G.A. (1992). How to make a blastocyst. Biochem. Cell Biol. 70, 849–55.CrossRefGoogle ScholarPubMed
Watson, A.J., Westhusin, M.E., De Sousa, P.A., Betts, D.H. & Barcroft, L.C. (1999). Gene expression regulating blastocyst formation. Theriogenology 51, 117–33.CrossRefGoogle ScholarPubMed
Wiekowski, M., Miranda, M., Nothias, J.Y. & DePamphilis, M.L. (1997). Changes in histone synthesis and modification at the beginning of mouse development correlate with the establishment of chromatin mediated repression of transcription. J. Cell Sci. 110, 1147–58.CrossRefGoogle ScholarPubMed
Wright, P.W., Bolling, L.C., Calvert, M.E., Sarmento, O.F., Berkeley, E.V., Shea, M.C., Hao, Z., Jayes, F.C., Bush, L.A., Shetty, J., Shore, A.N., Reddi, P.P., Tung, K.S., Samy, E., Allietta, M.M., Sherman, N.E., Herr, J.C. & Coonrod, S.A. (2003). ePAD, an oocyte and early embryo-abundant peptidylarginine deiminase-like protein that localizes to egg cytoplasmic sheets. Dev. Biol. 256, 73–88.CrossRefGoogle ScholarPubMed
Yoshioka, K., Suzuki, C., Tanaka, A., Anas, I.M. K & Iwamura, S. (2002). Birth of piglets derived from porcine zygotes cultured in a chemically defined medium. Biol. Reprod. 66, 112–19.CrossRefGoogle Scholar
Yung, B.Y., Busch, H. & Chan, P.K. (1985). Translocation of nucleolar phosphoprotein B23 (37kDa/pI5.1) induced by selective inhibitors of ribosome synthesis. Biochim. Biophys. Acta 826, 167–73.CrossRefGoogle Scholar
Zimmermann, U. & Viemken, J. (1982). Electric field-induced cell-to cell fusion. J. Membr. Biol. 67, 165–82.CrossRefGoogle ScholarPubMed