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BOR - Papers in Press, published online ahead of print February 27, 2008.
Biol Reprod 2008, 10.1095/biolreprod.107.067397
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BIOLOGY OF REPRODUCTION 78, 1073–1080 (2008)
DOI: 10.1095/biolreprod.107.067397
© 2008 by the Society for the Study of Reproduction, Inc.


research-article

Nuclear Histone Deacetylases Are Not Required for Global Histone Deacetylation During Meiotic Maturation in Porcine Oocytes1

Tsutomu Endo , Kiyoshi Kano , and Kunihiko Naito  2

Laboratory of Applied Genetics, Graduate School of Agriculture and Life Science, University of Tokyo, Tokyo 113-8657, Japan

ABSTRACT

Histone acetylation plays an important role in the regulation of chromatin structure and gene function. In mammalian oocytes, histones H3 and H4 are highly acetylated during the germinal vesicle (GV) stage, and global histone deacetylation takes place via a histone deacetylase (HDAC)-dependent mechanism after GV breakdown (GVBD). The presence of HDACs in the GVs of mammalian oocytes in spite of the high acetylation states of nuclear histones indicates that the HDACs in the nucleus are inactive but become activated after GVBD. However, the fluctuation pattern, the localization of HDAC activity during meiotic maturation and, moreover, the responsibility of nuclear HDACs for global histone deacetylation are still unknown. Here, we demonstrated using porcine oocytes that total HDAC activity was maintained throughout meiotic maturation, and high HDAC activity was observed in both the nucleus and the cytoplasm at the GV stage. The experiments with valproic acid (VPA), a specific class I HDAC inhibitor, revealed that the HDACs in GVs were class I, and those in the cytoplasm were other than class I. Interestingly, VPA had no effect on global histone deacetylation after GVBD, indicating that nuclear HDACs were not required for global histone deacetylation. To confirm this possibility, we removed the nuclei from immature oocytes, injected somatic cell nuclei into the enucleated oocytes, and showed that injected somatic cell nuclei were dramatically deacetylated after nuclear envelope breakdown. These results revealed that nuclear contents, including class I HDACs, are not required for the global histone deacetylation during meiosis, and that cytoplasmic HDACs other than class I are responsible for this process.

gamete biology, HDAC, kinases, meiosis, oocyte development


FOOTNOTES

1Supported by Grant-in-Aid for Scientific Research 19380155 to K.N., and by a Research Fellowship for Young Scientists grant 19-2573 from the Japan Society for the Promotion of Science to T.E.

Correspondence: 2Kunihiko Naito, Department of Animal Resource Sciences, Graduate School of Agricultural Sciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan. FAX: 81 3 5841 8191; e-mail: aknaito{at}mail.ecc.u-tokyo.ac.jp







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Copyright © 2008 by the Society for the Study of Reproduction.