EPIGENETIC MECHANISMS UNDERLYING DIFFERENTIATION DURING MAMMALIAN EMBRYONIC DEVELOPMENT Gametogenesis

the DNA double helix, is organized into a complex chromatin structure with the assistance of histone and nonhistone proteins. As such, chromatin is the physiologically relevant form of eukaryotic genomes. While it is largely uncontested that different genetic compositions of individual species underlie their unique physiology and final morphology, chromatin provides an additional layer for dictating the translation of genetic information into meaningful biological readouts (for review, see Strahl and Allis 2000; Jenuwein and Allis 2001; Felsenfeld and Groudine 2003). Increasing evidence underscores an emerging theme in biology wherein “epigenetic” mechanisms, defined as mechanisms operating outside of changes in DNA sequence, govern gene function by creating potentially heritable alternative states of chromatin. DNA methylation and covalent modifications of histones, such as methylation, acetylation, and phosphorylation, are thought to contribute to these chromatin states by serving as a platform that integrates cell differentiation signals and environmental cues as well as regulating the timely release of the appropriate genetic information (Cheung et al. 2000; Schreiber and Bernstein 2002). Several of the above histone modifications are readily reversible through enzymatic means; others are potentially static (Bannister et al. 2002; see below). One central problem that remains to be resolved is how these mechanisms are regulated either during normal developmental conditions or under various pathological conditions. EPIGENETIC MECHANISMS UNDERLYING DIFFERENTIATION DURING MAMMALIAN EMBRYONIC DEVELOPMENT