The Involvement of Chromatin in Mouse Embryo Development

Chromatin regulation may be important for early embryo development. It is believed cell potency and differentiation are controlled largely by epigenetic mechanisms, however, very little is known about the mechanisms and molecules involved in this process. We succeeded in implicating covalent histone residue modifications in the reprogramming events of early development. We discovered some histone modifications, namely; hyperacetylated histone H4, histone H3 arginine 17 methylation and histone H4 arginine 3 methylation are dynamic during the reprogramming period in mouse development. Two histone modifying enzymes were identified that play a role in modifying the epigenome of early embryos, and were found to be essential for development. The PAD family of enzymes was the first to be reported to have the ability to remove methyl marks from histones. MYST2 (HBO1 in human) was found to have a direct regulatory connection between p53-responsive stress signaling and histone acetylation, and this interaction defines a novel mechanism for coupling stress response signaling to chromatin structure. The results of these studies will have significant impact on understanding the basic science behind chromatin remodeling and also chromatin changes with respect to development. Our findings may have consequence in a broader range of issues and therapies such as cancer, congenital birth defects, somatic nuclear transfer, and stem cell therapy.

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