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First published online 17 August 2004
doi: 10.1242/jcs.01328
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Research Article |
1 Department of Cell Biology, University of Virginia Health Science Center, PO Box 800732, Charlottesville, VA 22908, USA
2 Laboratory of Chromatin Biology, The Rockefeller University, 230 York Avenue, New York, NY 10021, USA
3 Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA
* Author for correspondence (e-mail: scc2003{at}med.cornell.edu)
Accepted 25 May 2004
In order to investigate whether covalent histone modifications may be involved in early embryonic reprogramming events, changes in global levels of a series of histone tail modifications were studied during oocyte maturation and pre-implantation mouse development using indirect immunofluorescence and scanning confocal microscopy. Results showed that histone modifications could be classified into two strikingly distinct categories. The first contains stable `epigenetic' marks such as histone H3 lysine 9 methylation [Me(Lys9)H3], histone H3 lysine 4 methylation [Me(Lys4)H3] and histone H4/H2A serine 1 phosphorylation [Ph(Ser1)H4/H2A]. The second group contains dynamic and reversible marks and includes hyperacetylated histone H4, histone H3 arginine 17 methylation [Me(Arg17)H3] and histone H4 arginine 3 methylation [Me(Arg3)H4]). Our results also showed that removal of these marks in eggs and early embryos occurs during metaphase suggesting that the enzymes responsible for the loss of these modifications are probably cytoplasmic in nature. Finally, we provide data demonstrating that treatment of cellular histones with peptidylarginine deiminase (PAD) results in loss of staining for the histone H4 arginine 3 methyl mark, suggesting that PADs can reverse histone arginine methyl modifications.
Key words: Epigenetics, Histone modifications, Oocyte, Early embryo
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