[
International Worm Meeting,
2019]
Early embryonic cells are pluripotent, possessing the transient capacity to generate all the cells of an organism. A fundamental question in developmental biology concerns identifying the epigenetic factors that underlie this temporary developmental plasticity, as well as understanding how commitment to a specific cell lineage is achieved and maintained. How embryonic pluripotency is established, and whether development coordinates the restriction of cellular plasticity with the acquisition of cell fate is poorly understood. Recently, we have uncovered an unappreciated developmental regulation of the incorporation of key molecular carriers of epigenetic information, the replication-coupled histone H3 and histone variant, H3.3, during gametogenesis that influence the epigenetic organization in the early embryo, with a lasting effect on pluripotency and lineage commitment. To study the dynamics of endogenous histone genes throughout the C. elegans lineage, I have generated knock-in strains inserting protein-translational tags at the endogenous histone loci, as well as knock-out and point-mutations to study the developmental impact of the loss of tissue-specific histone incorporation. In doing so, I have uncovered a surprising difference in the epigenome established in the germline, and maintained during early embryogenesis, which incorporates low levels of canonical H3 incorporation in favor of the histone variant, H3.3. Furthermore, upon cellular differentiation, I have identified a 400-fold increase in canonical H3 incorporation in the somatic cell lineage. This onset of canonical H3 incorporation in late stage embryos correlates with a window of developmental plasticity which has been characterized in C. elegans embryonic blastomeres (Yuzyuk et al., 2009). Furthermore, as cells differentiate in late embryonic stages, transcriptionally silent heterochromatin begins to appear, this accumulation also correlates with a loss of both pluripotency and capacity to be reprogramed to alternative cell fates (Mutlu et al., 2018). I propose that global canonical H3 incorporation is developmentally programmed to restrict plasticity during embryogenesis, restricting cell fate choices.