Histone Deacetylase 1 Regulates Gene Expression During Mouse Preimplantation Embryogenesis.

Superimposed on the activation of embryonic genome in the preimplantation mouse embryo is the formation of a transcriptionally repressive state during the late two-cell stage. Several lines of evidence suggest that histone deacetylases (HDAC) may underlie the development of the transcriptionally repressive state during zygotic gene activation (ZGA) by mediating changes in the chromatin structure. In this study, we investigated expression and possible functions of Class I HDACs HDAC1, HDAC2, and HDAC3 during mouse preimplantation embryogenesis. We show that HDAC1 is likely a major deacetylase and its expression inversely correlates with changes of histone H4K5 acetylation state. RNAi-mediated reduction of HDAC1 leads to hyperacetylation of histone H4 and inhibited the incidence of development to the blastocyst stage even though expression of Hdac2 and Hdac3 is significantly induced in Hdac1-suppresssed embryos. RNAi-mediated reduction of HDAC2 has no noticeable effect on preimplantation development, suggesting that individual HDACs have distinct functions during preimplantation development. We also demonstrate that HDAC1 knockdown results in elevated levels of expression of a subset of genes that are normally repressed following genome activation and that this expression correlates with hyperacetylation of histone H4. Results of these experiments suggest that HDAC1 is involved in the development of a transcriptionally repressive state that initiates in 2-cell embryos.