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Regular Article |
a Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6018
b Kunming Institute of Zoology, Kunming, Yunnan Province, China
ABSTRACT
Superimposed on the activation of the embryonic genome in the preimplantation mouse embryo is the formation of a transcriptionally repressive state during the two-cell stage. This repression appears mediated at the level of chromatin structure, because it is reversed by inducing histone hyperacetylation or inhibiting the second round of DNA replication. We report that of more than 200 amplicons analyzed by mRNA differential display, about 45% of them are repressed between the two-cell and four-cell stages. This repression is scored as either a decrease in amplicon expression that occurs between the two-cell and four-cell stages or on the ability of either trichostatin A (an inhibitor of histone deacetylases) or aphidicolin (an inhibitor of replicative DNA polymerases) to increase the level of amplicon expression. Results of this study also indicate that about 16% of the amplicons analyzed likely are novel genes whose sequence doesn't correspond to sequences in the current databases, whereas about 20% of the sequences expressed during this transition likely are repetitive sequences. Lastly, inducing histone hyperacetylation in the two-cell embryos inhibits cleavage to the four-cell stage. These results suggest that genome activation is global and relatively promiscuous and that a function of the transcriptionally repressive state is to dictate the appropriate profile of gene expression that is compatible with further development.
First decision: 5 January 2001.
1 This research was supported by grant HD 22681 from the National Institutes of Health to R.M.S. J.M. was supported by the Major State Basic Research Development Program (G2000016108) of the Chinese Academy of Sciences to the Kunming Institute of Zoology, Kunming, Yunnan Province, China.
2 Correspondence: Richard Schultz, Department of Biology, University of Pennsylvania, 415 University Avenue, Philadelphia, PA 19104-6018. FAX: 215 898 8780; rschultz{at}mail.sas.upenn.edu
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