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Mol. Hum. Reprod. Advance Access originally published online on January 31, 2007
Molecular Human Reproduction 2007 13(3):141-148*; doi:10.1093/molehr/gal115
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© The Author 2007. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Histone acetylation and subcellular localization of chromosomal protein BRD4 during mouse oocyte meiosis and mitosis{dagger}

Takashi Nagashima1, Tetsuo Maruyama1,3, Masataka Furuya1, Takashi Kajitani1, Hiroshi Uchida1, Hirotaka Masuda1, Masanori Ono1, Toru Arase1, Keiko Ozato2 and Yasunori Yoshimura1

1 Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan 2 Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA

3 To whom correspondence should be addressed at: Department of Obstetrics and Gynecology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan. E-mail: tetsuo{at}sc.itc.keio.ac.jp

Most specific and general transcription factors (TFs) become dissociated from hypoacetylated mitotic chromosomes, which may contribute to transcriptional silencing during mitosis. Only some chromosomal proteins, such as bromodomain containing protein 4 (BRD4), have a potential to associate with mitotic chromosomes in a histone acetylation-dependent manner. It remains to be fully demonstrated whether similar displacement of nuclear factors takes place in meiotic oocytes whose chromosomes become globally deacetylated. To address this, we here examined the subcellular localization of BRD4 in conjunction with the acetylation status of histones in mouse oocytes. Immunofluorescence studies revealed that BRD4 preferentially localized to mitotic chromosomes in early embryos. In contrast, not only endogenous BRD4 but also exogenous BRD4 overexpressed by mRNA microinjection were displaced from meiotic chromosomes whose histones H3 and H4 were deacetylated. Treatment with trichostatin A (TSA), an inhibitor of histone deacetylases, induced histone hyperacetylation of meiotic chromosomes from which endogenous BRD4, however, remained dissociated. Finally, meiotic chromosomal localization of BRD4 could be achieved by BRD4 overexpression together with TSA-induced histone hyperacetylation. These results indicate that, unlike mitosis, histone acetylation is necessary but not sufficient for chromosomal localization of BRD4 during meiosis, suggesting that meiotic oocytes may have additional mechanism(s) for displacement of chromosomal proteins and TFs.

Key words: BRD4/bromodomain/histone acetylation/meiosis/oocyte

{dagger} Presented in part at the 22nd Annual Meeting of the European Society of Human Reproduction and Embryology.

* N.B. An error was made in the initial online pagination of Molecular Human Reproduction 13/3. The page span of this article was originally shown as 1–8. The publisher wishes to apologise for this error.


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[Abstract] [Full Text] [PDF]


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