Open chromatin is a conserved feature of pluripotent cells and is lost upon differentiation. As cells differentiate, the nucleus shrinks and chromatin undergoes global re-organization to generate domains of euchromatin and higher-order heterochromatin1,2. While much is known about chromatin organization at the local level, much less is known about the factors that govern large-scale nuclear organization and their regulation during embryogenesis. We have used ultrastructural and genomic approaches to track nuclear organization in C. elegans embryos as they transition from a developmentally plastic state towards differentiation. As embryos mature, higher-order heterochromatin emerges, visible as electron dense regions (EDRs) by electron microscopy. Concomitant with the appearance of EDRs, methylated histone H3 accumulates, and nucleosomes become more stable, as monitored by FAIRE (formaldehyde-assisted identification of regulatory elements)3. We find that the H3K9 methyltransferase MET-2 is required to build EDRs and promote loss of plasticity, but not to stabilize nucleosomes. These results highlight two apparently independent processes that generate a differentiated nucleus: i) generation of higher-order heterochromatin by MET-2, and ii) increased nucleosome stability. These changes may help focus the transcriptional machinery to discrete regions of open chromatin within differentiated cells.References1. Yuzyuk, T., Fakhouri, T.H.I., Kiefer, J., and Mango, S.E. (2009). The polycomb complex protein
mes-2/E(z) promotes the transition from developmental plasticity to differentiation in C. elegans embryos. Dev. Cell 16, 699-710.2. Gaspar-Maia, A., Alajem, A., Meshorer, E. & Ramalho-Santos, M. Open chromatin in pluripotency and reprogramming. Nat. Rev. Mol. Cell Biol. 12, 36-47 (2011).3. Giresi, P.G., Kim, J., McDaniell, R.M., Iyer, V.R., and Lieb, J.D. (2007). FAIRE (Formaldehyde-Assisted Isolation of Regulatory Elements) isolates active regulatory elements from human chromatin. Genome Res. 17, 877-885.